John Torgils Vaage

• Rasmussen, Tilde Harridsleff; Schikora-Rustad, Stine; Lorentzen, Åslaug Rudjord; Tran, Trung; Øverås, Mathias Herstad & Myhr, Kjell-Morten [Vis alle 22 forfattere av denne artikkelen] (2026). Low risk of severe COVID-19 in vaccinated people with multiple sclerosis: a nationwide Norwegian study. BMJ Neurology Open. 8(1). doi: 10.1136/bmjno-2026-001556. Fulltekst i vitenarkiv Vis sammendrag

  Background: We aimed to assess antibody responses and COVID-19 outcomes after vaccination in people with multiple sclerosis (pwMS) receiving disease-modifying therapies. Methods: NevroVAX is a Norwegian multicentre cohort study including 3559 pwMS and 449 healthy controls (HCs) who received at least one dose of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) or ChAdOx1 (AstraZeneca/Oxford) between January 2021 and December 2022. Data from records, registries, questionnaires and blood samples collected June 2021–November 2023 were analysed. Primary outcomes were humoral immune responses assessed by seroconversion (anti-spike and anti-receptor-binding domain (RBD) IgG ≥5 binding antibody units/mL). Secondary outcomes included quantitative anti-RBD IgG levels, breakthrough SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Associations with breakthrough infection were evaluated using multivariable logistic regression. Results: Among 3559 pwMS, 1201 received anti-CD20 monoclonal antibodies and 324 sphingosine-1-phosphate receptor (S1PR) modulators. After three vaccine doses, seroconversion was observed in 43.0% of anti-CD20-treated patients and 48.4% of S1PR-treated patients. In multivariable analysis, seroconversion was associated with lower risk of breakthrough infection (OR 0.67, 95% CI 0.58 to 0.78). During follow-up, 58 pwMS (1.6%) were hospitalised for COVID-19; 4 (0.1%) required non-invasive ventilatory support, no patients required invasive ventilation and no deaths occurred. Conclusions: Humoral vaccine responses were impaired in pwMS receiving anti-CD20 or S1PR therapies, but severe COVID-19 was rare. These findings support continued vaccination programmes and tailored protective measures for immunomodulated populations.

• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Vis alle 32 forfattere av denne artikkelen] (2025). An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models. Nature Communications. 16(1), s. 1–16. doi: 10.1038/s41467-025-59353-6. Fulltekst i vitenarkiv Vis sammendrag

  Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.

• Wolf, Asia-Sophia Fumika Michaela; Hammersbøen, Kristin Reine; Ørbo, Hilde Sofie Sager; Bhandari, Sabin; Solum, Guri & Kjønstad, Ingrid Fadum [Vis alle 30 forfattere av denne artikkelen] (2024). T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients on TNF inhibitor treatment: a prospective cohort study. EBioMedicine. 108. doi: 10.1016/j.ebiom.2024.105317. Fulltekst i vitenarkiv Vis sammendrag

  Background Understanding cellular responses to SARS-CoV-2 immunisations is important for informing vaccine recommendations in patients with inflammatory bowel disease (IBD) and other vulnerable patients on immunosuppressive therapies. This study investigated the magnitude and quality of T cell responses after multiple SARS-CoV-2 vaccine doses and COVID-19 breakthrough infection. Methods This prospective, observational study included patients with IBD and arthritis on tumour necrosis factor inhibitors (TNFi) receiving up to four SARS-CoV-2 vaccine doses. T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2–4 weeks after vaccinations and breakthrough infection to assess the frequency and polyfunctionality of responding cells, along with receptor-binding domain (anti-RBD) antibodies. Findings Between March 2, 2021, and December 20, 2022, 143 patients (118 IBD, 25 arthritis) and 73 healthy controls were included. In patients with either IBD or arthritis, humoral immunity was attenuated compared to healthy controls (median anti-RBD levels 3391 vs. 6280 BAU/ml, p = 0.008) after three SARS-CoV-2 vaccine doses. Patients with IBD had comparable quantities (median CD4 0.11% vs. 0.11%, p = 0.26, CD8 0.031% vs. 0.047%, p = 0.33) and quality (polyfunctionality score: 0.403 vs. 0.371, p = 0.39; 0.105 vs. 0.101, p = 0.87) of spike-specific T cells to healthy controls. Patients with arthritis had lower frequencies but comparable quality of responding T cells to controls. Breakthrough infection increased spike-specific CD8 T cell quality and T cell responses against non-spike peptides. Interpretation Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines.

• Kared, Hassen; Jyssum, Ingrid; Alirezaylavasani, Amin; Egner, Ingrid Marie; Tran, Trung & Tietze, Lisa [Vis alle 17 forfattere av denne artikkelen] (2024). Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study. Frontiers in Immunology. 15:1296273, s. 1–12. doi: 10.3389/fimmu.2024.1296273. Fulltekst i vitenarkiv Vis sammendrag

  Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays. Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells. Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.

• Alirezaylavasani, Amin; Egner, Ingrid Marie; Dahl, Tuva Børresdatter; Chopra, Adity; Kasahara, Taissa de Matos & Goll, Guro Løvik [Vis alle 15 forfattere av denne artikkelen] (2024). Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease. Clinical Immunology. ISSN 1521-6616. 271, s. 1–13. doi: 10.1016/j.clim.2024.110404. Fulltekst i vitenarkiv Vis sammendrag

  Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.

• Wüsthoff, Linda Elise Couëssurel; Lund-Johansen, Fridtjof; Henriksen, Kathleen; Wildendahl, Gull; Jacobsen, Jon-Aksel & Gomes, Leni [Vis alle 11 forfattere av denne artikkelen] (2024). Seroprevalence of SARS-CoV-2 and humoral immune responses to COVID-19 mRNA vaccines among people who use drugs - in the light of tailored mitigating strategies. Harm Reduction Journal. 21(1). doi: 10.1186/s12954-024-01023-9. Fulltekst i vitenarkiv Vis sammendrag

  Background During the initial wave of the COVID-19 pandemic, there was a surprisingly low incidence of SARS-CoV-2 among People Who Use Drugs (PWUD) in Oslo, Norway, despite their heightened vulnerability regarding risk of infection and severe courses of the disease.This study aims to investigate the seroprevalence of SARS-CoV-2 antibodies among PWUD, their antibody responses to relevant virus infections and COVID-19 mRNA vaccines, and their vaccination coverage compared to the general population. Methods Conducted as a prospective cohort study, data was collected from residents in six institutions for homeless PWUD and users of a low-threshold clinic for opioid agonist treatment. Ninety-seven participants were recruited for SARS-CoV-2 seroprevalence analysis. Additional two participants with known positive SARS-CoV-2 test results were recruited for further analyses. Twenty-five participants completed follow-up. Data included questionnaires, nasal swabs and blood samples. Data on vaccination coverage was obtained from the National Vaccine Register. Serologic methods included detection of antibodies to relevant virus proteins, neutralizing antibodies to SARS-CoV-2, antibodies to the full-length spike protein, and receptor-binding domain from SARS-CoV-2. Results Among PWUD, antibodies to SARS-CoV-2 were detected in 2 out of 97 samples before vaccines against SARS-CoV-2 were available, comparable to a 2.8% frequency in population-based screening. Levels of serum antibodies to seasonal coronaviruses and Epstein-Barr-Virus (EBV) in PWUD were similar to population-based levels. After the second vaccine dose, binding and neutralizing antibody levels to SARS-CoV-2 in PWUD were comparable to controls. Eighty-four of PWUD received at least one dose of COVID-19 mRNA vaccine, compared to 89% in the general population. Conclusion Results indicate that PWUD did not exhibit increased SARS-CoV-2 seroprevalence or elevated serum antibodies to seasonal coronaviruses and EBV. Moreover, vaccine responses in PWUD were comparable to controls, suggesting that vaccination is effective in conferring protection against SARS-CoV-2 also in this population.

• Alirezaylavasani, Amin; Skeie, Linda Gail; Egner, Ingrid Marie; Chopra, Adity; Dahl, Tuva Børresdatter & Prebensen, Christian Haugland [Vis alle 16 forfattere av denne artikkelen] (2024). Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections. npj Vaccines. 9(1), s. 1–15. doi: 10.1038/s41541-024-00972-3. Fulltekst i vitenarkiv Vis sammendrag

  The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm3). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.

• Ørbo, Hilde Sofie Sager; Kasahara, Taissa de Matos; Wolf, Asia-Sophia Fumika Michaela; Bjørlykke, Kristin Hammersbøen; Sexton, Joseph & Jyssum, Ingrid [Vis alle 24 forfattere av denne artikkelen] (2024). Humoral and cellular responses to a fifth bivalent SARS-CoV-2 vaccine dose in patients with immune-mediated inflammatory diseases on tumour necrosis factor inhibitors: a prospective cohort study. The Lancet Regional Health - Europe. 48. doi: 10.1016/j.lanepe.2024.101121. Fulltekst i vitenarkiv Vis sammendrag

  Background As most people now have established hybrid immunity, the need for regular, updated SARS-CoV-2 vaccine boosters in patients with immune-mediated inflammatory diseases (IMIDs) is unclear. The study aim was to assess humoral and cellular immunogenicity of a fifth bivalent vaccine dose in patients with IMID on tumour necrosis factor inhibitors (TNFi). Methods In the longitudinal, observational Nor-vaC study, we assessed anti-spike and neutralising antibodies against Wuhan, Omicron BA.1 and BA.4, as well as frequency and polyfunctionality of responding T cells, following a fourth monovalent and a fifth bivalent (BA.1 or BA.4/5) vaccine dose in patients with or without hybrid immunity using TNFi. Findings Between December 17, 2021, and June 20, 2023, 456 infection-naïve patients with IMIDs using TNFi received a fourth vaccine dose and were otherwise eligible for inclusion. A total of 373/456 (82%) received a fifth vaccine dose, of these 190/373 (51%) had hybrid immunity defined as having had COVID-19 between the fourth and fifth dose. In patients with hybrid immunity, the fifth dose did not induce improved humoral responses compared to infection, neither with BA.1 (median anti-spike antibody concentrations 23,244 IU/ml (IQR 15,138–45,233) vs 36,341 IU/ml (11,887–53,710), p = 0.52) nor BA.4/5 (31,693 IU/ml (15,176–54,186), p = 0.30). Comparison of neutralising antibodies yielded similar results. In infection-naïve patients, a fifth BA.4/5 vaccine, but not the BA.1, induced slightly higher humoral responses (18,890 IU/ml (6494–50,211)) compared to the fourth dose (7304 IU/ml (3245–17,260), p < 0.0001). CD8 T cell responses remained stable following a fourth dose (median frequency of spike-specific cells 0.039% (IQR 0.010–0.14)), infection (0.058% (0.026–0.17)) and a fifth dose (0.058% (0.013–0.20). Interpretation In patients on TNFi with hybrid immunity, there was no immunological benefit of an updated fifth SARS-CoV-2 booster dose. Stable CD8 cellular responses following four doses indicate established protective immunity. Patients whose only risk factor is TNFi may in future follow vaccine recommendations for the general population.

• Ørbo, Hilde Sofie Sager; Hammersbøen, Kristin Reine; Sexton, Joseph; Jyssum, Ingrid; Tveter, Anne Therese & Christensen, Ingrid Egeland [Vis alle 18 forfattere av denne artikkelen] (2024). Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study. RMD Open. 10(2). doi: 10.1136/rmdopen-2023-003545. Fulltekst i vitenarkiv Vis sammendrag

  Objectives To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. Methods IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2–5 weeks post-immunisation. Results Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)). Conclusion Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals. Trial registration number NCT04798625.

• Tunheim, Gro; Fossum, Even; Robertson, Anna Hayman; Rø, Gunnar Øyvind Isaksson; Chopra, Adity & Vaage, John T. [Vis alle 13 forfattere av denne artikkelen] (2024). Characterization of the SARS-CoV-2 antibody landscape in Norway in the late summer of 2022: high seroprevalence in all age groups with patterns of primary Omicron infection in children and hybrid immunity in adults. BMC Infectious Diseases. 24:841(1), s. 1–20. doi: 10.1186/s12879-024-09670-w. Fulltekst i vitenarkiv Vis sammendrag

  Background According to Norwegian registries, 91% of individuals ≥ 16 years had received ≥ 1 dose of COVID-19 vaccine by mid-July 2022, whereas less than 2% of children < 12 years were vaccinated. Confirmed COVID-19 was reported for 27% of the population, but relaxation of testing lead to substantial underreporting. We have characterized the humoral immunity to SARS-CoV-2 in Norway in the late summer of 2022 by estimating the seroprevalence and identifying antibody profiles based on reactivity to Wuhan or Omicron-like viruses in a nationwide cross-sectional collection of residual sera, and validated our findings using cohort sera. Methods 1,914 anonymized convenience sera and 243 NorFlu-cohort sera previously collected from the Oslo-area with reported infection and vaccination status were analyzed for antibodies against spike, the receptor-binding domain (RBD) of the ancestral Wuhan strain and Omicron BA.2 RBD, and nucleocapsid (N). Samples were also tested for antibodies inhibiting RBD-ACE2 interaction. Neutralization assays were performed on subsets of residual sera against B.1, BA.2, XBB.1.5 and BQ.1.1. Results The national seroprevalence estimate from vaccination and/or infection was 99.1% (95% CrI 97.0-100.0%) based on Wuhan (spike_W and RBD_W) and RBD_BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD_BA2 than RBD_W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD_BA2 antibodies compared to Wuhan-antibodies alone. 50.3% (95% CI 45.0-55.5%) of residual sera from children and 38.1% (95% CI 36.0-40.4%) of all residual sera were positive for anti-N-antibodies. By combining measurements of binding- and ACE2-RBD-interaction-inhibiting antibodies, reactivity profiles indicative of infection and vaccination history were identified and validated using cohort sera. Residual sera with a profile indicative of hybrid immunity were able to neutralize newer Omicron variants XBB.1.5 and BQ.1.1. Conclusions By late summer of 2022, most of the Norwegian population had antibodies to SARS-CoV-2, and almost all children had been infected. Antibody profiles indicated that children mostly had experienced a primary Omicron infection, while hybrid immunity was common among adults. The finding that sera displaying hybrid immunity could neutralize newer Omicron variants indicates that Wuhan-like priming of the immune response did not have a harmful imprinting effect and that infections induce cross-reacting antibodies against future variants.

• Kared, Hassen; Alirezaylavasani, Amin; Lund, Kathrine Persgård; Chopra, Adity; Tietze, Lisa & Kasahara, Taissa de Matos [Vis alle 17 forfattere av denne artikkelen] (2023). Hybrid and SARS-CoV-2-vaccine immunity in kidney transplant recipients. EBioMedicine. 97. doi: 10.1016/j.ebiom.2023.104833. Fulltekst i vitenarkiv Vis sammendrag

  Background Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection. Methods We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3–4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors. Findings After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG+ B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5–6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses. Interpretation Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population.

• Nissen-Meyer, Lise Sofie Haug; Macpherson, Magnhild Eide; Skeie, Linda Gail; Hvalryg, Marte; LLOHN, ABID HUSSAIN & Steinsvåg, Tine Torsvik [Vis alle 17 forfattere av denne artikkelen] (2023). Covid-19-pasienter behandlet med rekonvalesensplasma. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(11). doi: 10.4045/tidsskr.22.0577. Fulltekst i vitenarkiv Vis sammendrag

  BAKGRUNN I Norge er behandling med covid-19-rekonvalesensplasma gitt gjennom NORPLASMA-prosjektet. I begynnelsen ble behandlingen tilbudt kritisk syke pasienter etter individuell vurdering, men fra desember 2020 ble indikasjonen begrenset til kritisk syke pasienter med immunsvikt. Vi beskriver her kliniske karakteristika, komorbiditet og mortalitet hos pasienter som fikk rekonvalesensplasma i disse to periodene. MATERIALE OG METODE I perioden 22.4.2020–30.3.2022 ble 79 pasienter inkludert i observasjonsstudiene NORPLASMA MONITOR og Norwegian SARS-CoV-2-studien. Pasientene hadde mottatt totalt 193 enheter med rekonvalesensplasma ved 15 norske sykehus/sykehjem: 62 i Helse Sør-Øst, 8 i Helse Vest og 9 i Helse Midt-Norge. Opplysninger om immunstatus, komorbiditet og sykdomsforløp ble registrert fra pasientjournalen etter skriftlig samtykke. RESULTATER Av 79 pasienter med median alder 65 år (interkvartilbredde 51–73) som fikk behandling med rekonvalesensplasma, døde 31 (39 %) under sykehusoppholdet. 59 pasienter hadde immunsvikt, og blant disse døde 20 i sykehus, mot 11 av 20 antatt immunkompetente. Median antall komorbiditeter var 2 (interkvartilbredde 1–4). Pasientene fikk i median 2 plasmaenheter (min–maks 1–21). To av pasientene utviklet milde allergiske hudreaksjoner. FORTOLKNING Rekonvalesensplasma ble godt tolerert av pasienter med covid-19. Immunsviktpasienter hadde muligens effekt av behandlingen, med lavere dødelighet i denne gruppen enn blant antatt immunkompetente.

• Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; König, Marton; Øverås, Mathias Herstad; Solum, Guri & Kjønstad, Ingrid Fadum [Vis alle 18 forfattere av denne artikkelen] (2023). T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis. JCI Insight. 8(12), s. 1–14. doi: 10.1172/jci.insight.165111. Fulltekst i vitenarkiv Vis sammendrag

  Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

• Nissen-Meyer, Lise Sofie Haug; Steinsvåg, Christine Torsvik; Fenstad, Mona H.; Sørvoll, Ingvild Hausberg; Hvalryg, Marte & Titze, Thomas Larsen [Vis alle 20 forfattere av denne artikkelen] (2023). Rekonvalesensplasma mot covid-19 fremstilt fra norske blodgivere. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(11), s. 953–957. doi: 10.4045/tidsskr.22.0180. Fulltekst i vitenarkiv Vis sammendrag

  BAKGRUNN I Norge er behandling med covid-19-rekonvalesensplasma gitt gjennom NORPLASMA-prosjektet. I begynnelsen ble behandlingen tilbudt kritisk syke pasienter etter individuell vurdering, men fra desember 2020 ble indikasjonen begrenset til kritisk syke pasienter med immunsvikt. Vi beskriver her kliniske karakteristika, komorbiditet og mortalitet hos pasienter som fikk rekonvalesensplasma i disse to periodene. MATERIALE OG METODE I perioden 22.4.2020–30.3.2022 ble 79 pasienter inkludert i observasjonsstudiene NORPLASMA MONITOR og Norwegian SARS-CoV-2-studien. Pasientene hadde mottatt totalt 193 enheter med rekonvalesensplasma ved 15 norske sykehus/sykehjem: 62 i Helse Sør-Øst, 8 i Helse Vest og 9 i Helse Midt-Norge. Opplysninger om immunstatus, komorbiditet og sykdomsforløp ble registrert fra pasientjournalen etter skriftlig samtykke.RESULTATER Av 79 pasienter med median alder 65 år (interkvartilbredde 51–73) som fikk behandling med rekonvalesensplasma, døde 31 (39 %) under sykehusoppholdet. 59 pasienter hadde immunsvikt, og blant disse døde 20 i sykehus, mot 11 av 20 antatt immunkompetente. Median antall komorbiditeter var 2 (interkvartilbredde 1–4). Pasientene fikk i median 2 plasmaenheter (min–maks 1–21). To av pasientene utviklet milde allergiske hudreaksjoner. FORTOLKNING Rekonvalesensplasma ble godt tolerert av pasienter med covid-19. Immunsviktpasienter hadde muligens effekt av behandlingen, med lavere dødelighet i denne gruppen enn blant antatt immunkompetente.

• Åsberg, Anders; Hovd, Markus Herberg; Kjellevold, Stig Arne; Stenehjem, Aud Eldrid; Wien, Tale Norbye & Broch, Lars Ulrik [Vis alle 15 forfattere av denne artikkelen] (2023). Humoral Response After 6 or More Successive Doses of SARS-CoV-2 mRNA Vaccines in Kidney Transplant Recipients-Should We Keep Vaccinating? Transplantation. ISSN 0041-1337. 107(10), s. e279–e280. doi: 10.1097/TP.0000000000004732. Fulltekst i vitenarkiv
• Jørgensen, Kristin Kaasen; Høivik, Marte Lie; Chopra, Adity; Benth, Jurate Saltyte; Ricanek, Petr & Moum, Bjørn Allan [Vis alle 18 forfattere av denne artikkelen] (2023). Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(8), s. 874–882. doi: 10.1080/00365521.2023.2177884. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. Materials and methods This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. Results In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. Conclusions Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

• Gainullin, Murat; Federico, Lorenzo; Osen, Julie Røkke; Chaban, Viktoriia; Kared, Hassen & Alirezaylavasani, Amin [Vis alle 18 forfattere av denne artikkelen] (2023). People who use drugs show no increase in pre-existing T-cell cross-reactivity toward SARS-CoV-2 but develop a normal polyfunctional T-cell response after standard mRNA vaccination. Frontiers in Immunology. 14:1235210, s. 1–13. doi: 10.3389/fimmu.2023.1235210. Fulltekst i vitenarkiv Vis sammendrag

  People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4 + and CD8 + T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.

• Hovd, Markus Herberg; Åsberg, Anders; Munthe, Ludvig Andre; Heldal, Kristian; Reisæter, Anna Varberg & Vaage, John T. [Vis alle 8 forfattere av denne artikkelen] (2023). Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study. EClinicalMedicine. 60. doi: 10.1016/j.eclinm.2023.102035. Fulltekst i vitenarkiv Vis sammendrag

  Background Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. Methods We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4–10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. Findings The study included 3607 KTRs (59 [48–70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3–4] vaccines (range 2–6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31–57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Interpretation Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic.

• Federico, Lorenzo; Tvedt, Tor Henrik Anderson; Gainullin, Murat; Osen, Julie Røkke; Chaban, Viktoriia & Lund, Kathrine Persgård [Vis alle 19 forfattere av denne artikkelen] (2023). Robust spike-specific CD4⁺ and CD8⁺ T cell responses in SARS-CoV-2 vaccinated hematopoietic cell transplantation recipients: a prospective, cohort study. Frontiers in Immunology. 14. doi: 10.3389/fimmu.2023.1210899. Fulltekst i vitenarkiv Vis sammendrag

  Poor overall survival of hematopoietic stem cell transplantation (HSCT) recipients who developed COVID-19 underlies the importance of SARS-CoV-2 vaccination. Previous studies of vaccine efficacy have reported weak humoral responses but conflicting results on T cell immunity. Here, we have examined the relationship between humoral and T cell response in 48 HSCT recipients who received two doses of Moderna’s mRNA-1273 or Pfizer/BioNTech’s BNT162b2 vaccines. Nearly all HSCT patients had robust T cell immunity regardless of protective humoral responses, with 18/48 (37%, IQR 8.679-5601 BAU/mL) displaying protective IgG anti-receptor binding domain (RBD) levels (&amp;gt;2000 BAU/mL). Flow cytometry analysis of activation induced markers (AIMs) revealed that 90% and 74% of HSCT patients showed reactivity towards immunodominant spike peptides in CD8 + and CD4 + T cells, respectively. The response rate increased to 90% for CD4 + T cells as well when we challenged the cells with a complete set of overlapping peptides spanning the entire spike protein. T cell response was detectable as early as 3 months after transplant, but only CD4 + T cell reactivity correlated with IgG anti-RBD level and time after transplantation. Boosting increased seroconversion rate, while only one patient developed COVID-19 requiring hospitalization. Our data suggest that HSCT recipients with poor serological responses were protected from severe COVID-19 by vaccine-induced T cell responses.

• Meyer, Saskia; Blaas, Isaac; Bollineni, Ravi Chand; Delic-Sarac, Marina; Tran, Trung & Knetter, Cathrine [Vis alle 20 forfattere av denne artikkelen] (2023). Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants. Cell reports. 42(1). doi: 10.1016/j.celrep.2023.111995. Fulltekst i vitenarkiv Vis sammendrag

  The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.

• Bjørlykke, Kristin H.; Ørbo, Hilde Sofie Sager; Tveter, Anne Therese; Jyssum, Ingrid; Sexton, Joseph & Tran, Trung [Vis alle 21 forfattere av denne artikkelen] (2022). Four SARS-CoV-2 vaccine doses or hybrid immunity in patients on immunosuppressive therapies: a Norwegian cohort study. The Lancet Rheumatology. 5(1), s. e36–e46. doi: 10.1016/S2665-9913(22)00330-7. Fulltekst i vitenarkiv Vis sammendrag

  Background Data on response and safety of repeated vaccinations and hybrid immunity in patients with immune-mediated inflammatory diseases on immunosuppressive therapy is needed to further develop vaccination strategies in this vulnerable population. This study aimed to evaluate hybrid immunity and humoral immune response and safety of four SARS-CoV-2 vaccine doses in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. Methods This prospective observational Norwegian study of vaccine response to COVID-19 (Nor-vaC) included adult patients aged 18 years and older with immune-mediated inflammatory diseases (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis) on immunosuppressive therapy, who had received four SARS-CoV-2 vaccine doses (vaccine group) or three vaccine doses followed by COVID-19 (hybrid group), and healthy controls receiving three vaccine doses (control group). Patients were recruited from the Division of Rheumatology at Diakonhjemmet Hospital, Oslo, and the Department of Gastroenterology at Akershus University Hospital, Lørenskog. Patients who had COVID-19 before the third vaccine dose, and patients with allergies or intolerances to elements of the vaccine were excluded. Antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD antibodies) were assessed 2–4 weeks following vaccination or COVID-19. This study is registered at Clinialtrials.gov, NCT04798625. Findings Between Nov 12, 2021, and April 19, 2022, 1458 participants with immune-mediated inflammatory diseases provided post-vaccination samples at 2–4 weeks following a third vaccine dose. After 544 participants were excluded, 715 (78%) of the remaining 914 participants received the fourth dose of the vaccine, and of these, 536 (75%) provided post-vaccination samples 2–4 weeks after their fourth vaccination (vaccine group). 199 (22%) of the 914 had COVID-19 after their third dose of the vaccine and of these, 167 (84%) provided samples (hybrid group). 256 of the eligible 703 patients had rheumatoid arthritis, 107 had spondyloarthritis, 115 had psoriatic arthritis, 130 had Crohn's disease, and 95 had ulcerative colitis). Median age was 56 years [IQR 45–65], 398 (57%) were women, and 305 (43%) were men. Patients in the vaccine group had higher anti-RBD antibody concentrations following the fourth vaccine dose (median 6192 BAU/ml [IQR 2878–11 243]) than after the third dose (median 5087 BAU/ml [1250–9081]; p< 0·0001), but lower antibody concentrations than the control group following the third dose (median 7595 BAU/ml [5916–12 001]; p< 0·0001). Antibody concentrations were higher in the patients in the hybrid group (23 548 BAU/ml [IQR 11 440–35 935]) than in the vaccine group (p<0·0001). No difference was found in antibody concentrations between the fourth dose of BNT162b2 (full-dose) and mRNA-1273 (half-dose). Patients and controls had a comparable safety profile after both three and four vaccine doses. Interpretation Vaccine boosters improve humoral immune responses and are safe in patients with immune-mediated inflammatory diseases on immunosuppressive therapy, and administration should be considered regularly in this patient group. Hybrid immunity with omicron induces a strong humoral response suggesting longer intervals between booster doses in this patient group.

• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Vis alle 40 forfattere av denne artikkelen] (2022). Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants. npj Vaccines. 7(1). doi: 10.1038/s41541-022-00586-7. Fulltekst i vitenarkiv Vis sammendrag

  Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

• Ibsen, Jostein Holen; Chopra, Adity; Vaage, Eline Benno; Vaage, John T.; Lund-Johansen, Fridtjof & Lundin, Knut (2022). Immune responses to SARS-CoV-2 vaccines in celiac disease. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 00(0). doi: 10.1080/00365521.2022.2114809. Fulltekst i vitenarkiv Vis sammendrag

  Background and aims SARS-CoV-2 infection and development of the disease COVID-19 is a serious threat to our society. Effective vaccines have now entered the market, but most patient populations were not included in the registration clinical trials. There is evidence that patients with celiac disease (CeD) have reduced effect of vaccines such as the hepatitis B vaccine. Hence, we investigated the humoral response to SARS-CoV-2 vaccines (Chadox1, Comirnaty and Spikevax) in CeD patients and healthy controls. Methods CeD patients from a patient registry at Oslo University Hospital were invited to donate serum samples before and after vaccination. We sent out 1537 invitations and received paired samples from 85 individuals. These were compared with similar samples from 238 healthy controls. Sera were analyzed for antibodies to the Spike protein from SARS-CoV2 and the receptor-binding domain. The results where then converted into binding antibody units (BAU)/ml to compare. Results Prevaccination samples showed that very few patients had been earlier exposed to Sars-CoV2 and the antibody levels were low. Postvaccination analysis showed overlap of antibody levels between CeD and healthy controls. On average, the CeD patient group had 5555.0 BAU/ml (330.1 SD) while the average in healthy controls was 5419 (184.7 SD). Conclusion The humoral response to SARS-CoV-2 vaccines in CeD patients is similar to that observed in healthy controls.

• Kared, Hassen; Wolf, Asia-Sophia Fumika Michaela; Alirezaylavasani, Amin; Ravussin, Anthony; Solum, Guri & Tran, Trung [Vis alle 17 forfattere av denne artikkelen] (2022). Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults. Nature Communications. 13(1). doi: 10.1038/s41467-022-31888-y. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event have robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Individuals with Omicron SARS-CoV-2 breakthrough infections have significantly increased activated SARS-CoV-2 wild type Spike-specific cytotoxic T cells, activated follicular helper (T FH ) cells, functional T cell responses, boosted humoral responses, and rapid release of Spike and RBD-specific IgG + B cell plasmablasts and memory B cells into circulation. Omicron breakthrough infection affords significantly increased de novo memory T cell responses to non-Spike viral antigens. Concerted T and B cell responses may provide durable and broad immunity.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Tran, Trung; Sexton, Joseph & Provan, Sella Aarrestad [Vis alle 22 forfattere av denne artikkelen] (2022). Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy. Arthritis & Rheumatology. ISSN 2326-5191. 74(8), s. 1321–1332. doi: 10.1002/art.42153. Fulltekst i vitenarkiv Vis sammendrag

  Objective Immunogenicity and safety following receipt of the standard SARS–CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS–CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. Methods Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS–CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS–CoV-2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS–Cov-2 spike protein, were allotted a third vaccine dose. Results A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. Conclusion IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

• Søraas, Arne Vasli; Grødeland, Gunnveig; Granerud, Beathe Kiland; Ueland, Thor; Lind, Andreas & Fevang, Børre [Vis alle 32 forfattere av denne artikkelen] (2022). Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity. Frontiers in Immunology. 13:964525, s. 1–12. doi: 10.3389/fimmu.2022.964525. Fulltekst i vitenarkiv Vis sammendrag

  Background: Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals. Methods: We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. Findings: Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters. Interpretation: The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Christensen, Ingrid Egeland & Tran, Trung [Vis alle 20 forfattere av denne artikkelen] (2022). Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. RMD Open. 8(2). doi: 10.1136/rmdopen-2022-002417. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. Methods Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2–4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2–4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. Results 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138–8732) compared with 4495 (1591–6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150–4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p<0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. Conclusions This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. Trial registration number NCT04798625.

• Riise, Jon; Meyer, Saskia; Blaas, Isaac; Chopra, Adity; Tran, Trung & Delic-Sarac, Marina [Vis alle 22 forfattere av denne artikkelen] (2022). Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination. British Journal of Haematology. ISSN 0007-1048. 197(6), s. 697–708. doi: 10.1111/bjh.18149. Fulltekst i vitenarkiv Vis sammendrag

  B-cell depletion induced by anti-cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, but effects on CD8 T-cell responses are unknown. Here, we investigated humoral and CD8 T-cell responses following two vaccinations in patients with lymphoma undergoing anti-CD20-mAb therapy as single agent or in combination with chemotherapy or other anti-neoplastic agents during the last 9 months prior to inclusion, and in healthy age-matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor-binding domain of the SARS-CoV-2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T-cell responses against prevalent human leucocyte antigen (HLA) class I SARS-CoV-2 epitopes were determined by peptide-HLA multimer analysis. Strong CD8 T-cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS-CoV-2-vaccinated, anti-CD20-treated patients with lymphoma, their CD8 T-cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B-cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID-19) vaccines, and development of vaccines aimed at eliciting T-cell responses to non-Spike epitopes might provide improved protection.

• König, Marton; Torgauten, Hilde Marie; Tran, Trung; Holmøy, Trygve; Vaage, John T. & Lund-Johansen, Fridtjof [Vis alle 7 forfattere av denne artikkelen] (2022). Immunogenicity and Safety of a Third SARS-CoV-2 Vaccine Dose in Patients with Multiple Sclerosis and Weak Immune Response after COVID-19 Vaccination. JAMA Neurology. ISSN 2168-6149. 79(3), s. 307–309. doi: 10.1001/jamaneurol.2021.5109. Fulltekst i vitenarkiv
• Christensen, Ingrid Egeland; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Tran, Trung & Mjaaland, Siri [Vis alle 19 forfattere av denne artikkelen] (2022). The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study. BMC Medicine. 20(1), s. 1–13. doi: 10.1186/s12916-022-02587-8. Fulltekst i vitenarkiv Vis sammendrag

  Background The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. Methods IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6–48 days, second within 49–123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. Results A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn’s disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15–24] and 97 days [87–105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018–6068] in patients and 6187 BAU/ml [4105–7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58–1053] in patients and 1520 BAU/ml [979–3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was − 83% in patients and − 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls − 4.9 (95% CI − 7.4 to − 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. Conclusions Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

• Tunheim, Gro; Rø, Gunnar Øyvind Isaksson; Chopra, Adity; Aase, Audun; Kran, Anne-Marte Bakken & Vaage, John T. [Vis alle 8 forfattere av denne artikkelen] (2022). Prevalence of antibodies against SARS-CoV-2 in the Norwegian population, August 2021. Influenza and Other Respiratory Viruses. ISSN 1750-2640. 16(6), s. 1004–1013. doi: 10.1111/irv.13024. Fulltekst i vitenarkiv Vis sammendrag

  Background One year into the COVID-19 pandemic, the cumulative number of confirmed COVID-19 cases in Norway was still low. In January 2021, when the Norwegian COVID-19 vaccination campaign started, the national seroprevalence estimate of SARS-CoV-2 antibodies was 3.2%. We have conducted a nationwide cross-sectional study in August 2021 to investigate the overall prevalence of SARS-CoV-2 antibodies in Norway after 8 months of COVID-19 mass vaccination and a third wave of SARS-CoV-2 infection. Methods Residual sera were collected from laboratories across Norway in August 2021. In IgG antibodies against the spike protein, the spike receptor binding domain (RBD) and the nucleocapsid protein of SARS-CoV-2 were measured by a bead-based flow cytometric assay. Results In total, 1926 residual sera were collected from individuals aged 0–98 years; 55.1% were from women. The overall national estimated seroprevalence from vaccination and/or infection was 62.6% (credible interval [CrI] 60.1%–65.2%) based on having antibodies against both spike and RBD. Estimated seroprevalence increased with age. Among all samples, 11.7% had antibodies against nucleocapsid. For unvaccinated children <12 years, the seroprevalence estimate due to SARS-CoV-2 infection was 12.5% (95% CrI 9.3%–16.1%). Of seropositive samples from the unvaccinated children, 31.9% lacked anti-nucleocapsid antibodies. Conclusions The high overall SARS-CoV-2 seroprevalence estimates are in line with Norwegian registry data. Vaccination, not infection, contributed the most to the high seroprevalence in August 2021. Lack of antibodies against nucleocapsid should not automatically be interpreted as absence of previous infection as this could lead to underestimation of COVID-19 cases in seroprevalence studies.

• Jyssum, Ingrid; Kared, Hassen; Tran, Trung; Tveter, Anne Therese; Provan, Sella Aarrestad & Sexton, Joseph [Vis alle 22 forfattere av denne artikkelen] (2021). Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study. The Lancet Rheumatology. 00. doi: 10.1016/S2665-9913(21)00394-5. Fulltekst i vitenarkiv Vis sammendrag

  Background In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. Methods This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2–4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7–10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. Findings Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222–324] in responders vs 107 days [80–152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. Interpretation This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6–9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response.

• Tunheim, Gro; Rø, Gunnar Øyvind Isaksson; Tran, Trung; Kran, Anne-Marte Bakken; Andersen, Jan Terje & Vaage, Eline Benno [Vis alle 10 forfattere av denne artikkelen] (2021). Trends in seroprevalence of SARS-CoV-2 and infection fatality rate in the Norwegian population through the first year of the COVID-19 pandemic. Influenza and Other Respiratory Viruses. ISSN 1750-2640. 16(2), s. 204–212. doi: 10.1111/irv.12932. Fulltekst i vitenarkiv Vis sammendrag

  Background Infection with the novel coronavirus SARS-CoV-2 induces antibodies that can be used as a proxy for COVID-19. We present a repeated nationwide cross-sectional study assessing the seroprevalence of SARS-CoV-2, the infection fatality rate (IFR), and infection hospitalization rate (IHR) during the first year of the pandemic in Norway. Methods Residual serum samples were solicited in April/May 2020 (Round 1), in July/August 2020 (Round 2) and in January 2021 (Round 3). Antibodies against SARS-CoV-2 were measured using a flow cytometer-based assay. Aggregate data on confirmed cases, COVID-19-associated deaths and hospitalizations were obtained from the Emergency preparedness registry for COVID-19 (Beredt C19), and the seroprevalence estimates were used to estimate IFR and IHR. Results Antibodies against SARS-CoV-2 were measured in 4840 samples. The estimated seroprevalence increased from 0.8% (95% credible interval [CrI] 0.4%–1.3%) after the first wave of the pandemic (Rounds 1 and 2 combined) to 3.2% (95% CrI 2.3%–4.2%) (Round 3). The IFR and IHR were higher in the first wave than in the second wave and increased with age. The IFR was 0.2% (95% CrI 0.1%–0.3%), and IHR was 0.9% (95% CrI 0.6%–1.5%) for the second wave. Conclusions The seroprevalence estimates show a cumulative increase of SARS-CoV-2 infections over time in the Norwegian population and suggest some under-recording of confirmed cases. The IFR and IHR were low, corresponding to the relatively low number of COVID-19-associated deaths and hospitalizations in Norway. Most of the Norwegian population was still susceptible to SARS-CoV-2 infection after the first year of the pandemic.

• König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, Trung; Schikora-Rustad, Stine & Vaage, Eline Benno [Vis alle 22 forfattere av denne artikkelen] (2021). Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. doi: 10.1136/jnnp-2021-327612. Fulltekst i vitenarkiv Vis sammendrag

  Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

• Kjeldsen-Kragh, Jens; Titze, Thomas Larsen; Lie, Benedicte Alexandra; Vaage, John T. & Kjær, Mette (2019). HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a-immunized women. Blood Advances. ISSN 2473-9529. 3(7), s. 945–951. doi: 10.1182/bloodadvances.2019032227. Fulltekst i vitenarkiv Vis sammendrag

  HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a–immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB3*01:01 allele on anti-HPA-1a levels (global P value [Pglobal] = .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother’s HLA-DRB3*01:01 allele on the platelet count of the newborn (Pglobal = .0155). Median (range) neonatal platelet counts were 241 × 109/L (59 × 109/L to 393 × 109/L), 107 × 109/L (4 × 109/L to 387 × 109/L) and 32 × 109/L (4 × 109/L to 352 × 109/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a–immunized women.

• Dai, Ke-Zheng; Ryan, James C.; Naper, Christian & Vaage, John T. (2018). Identification of MHC class Ib ligands for stimulatory and inhibitory Ly49 receptors and induction of potent NK cell alloresponses in rats. Journal of Immunology. ISSN 0022-1767. 200(8), s. 2847–2859. doi: 10.4049/jimmunol.1701464. Fulltekst i vitenarkiv Vis sammendrag

  Early studies indicate that rats may have a repertoire of MHC class Ib–reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia–like structural features encoded from the first telomeric MHC class Ib gene cluster, RT1-CE, which is syntenic with the H2-D/H2-L/H2-Q cluster in mice. The activating Ly49s4 receptor and its inhibitory counterparts, Ly49i4 and Ly49i3, reacted with all allelic variants of RT1-U, whereas Ly49s5 and Ly49i5 were specific for RT1-Eu. NK cell cytolytic responses were predictably activated and inhibited, and potent in vivo NK alloresponses were induced by repeated MHC class Ib alloimmunizations. Additional Ly49–class Ib interactions, including RT1-Cl with the Ly49s4/Ly49i4/Ly49i3 group of receptors, were characterized using overexpressed receptor/ligand pairs, in vitro functional assays, and limited mutational analyses. Obvious, as well as subtle, Ly49–class Ib interactions led to ligand-induced receptor calibration and NK subset expansions in vivo. Together, these studies suggest that in vivo NK alloresponses are controlled by pleomorphic Ly49–class Ib interactions, some of which may not be easily detectable in vitro.

• Sudworth, Amanda; Vaage, John T.; Inngjerdingen, Marit & Kveberg, Lise (2017). Frontline Science: A hyporesponsive subset of rat NK cells negative for Ly49s3 and NKR-P1B are precursors to the functionally mature NKR-P1B+ subset. Journal of Leukocyte Biology. ISSN 0741-5400. 102(6), s. 1289–1298. doi: 10.1189/jlb.1HI0517-177RR. Fulltekst i vitenarkiv Vis sammendrag

  Rat NK cells are divided into major subsets expressing either Ly49 receptors or the inhibitory NKR‐P1B receptor in conjunction with NKG2A/C/E receptors. A minor subset of NKp46+ cells lacking expression of both Ly49 receptors and NKR‐P1B is present in blood and spleen and is associated with decreased functional competence. We hypothesized that this subset may represent precursors to Ly49+ and/or NKR‐P1B+ NK cells. When cultured in vitro in IL‐2 and IL‐15 or adoptively transferred to syngeneic hosts, a portion of NKR‐P1B−Ly49s3− cells transformed to express NKR‐P1B, but very little Ly49s3. Acquisition of NKR‐P1B by NKR‐P1B−Ly49s3− cells coincided with increased degranulation. In addition, although NKR‐P1B−Ly49s3− cells highly proliferate, proliferative activity was reduced upon acquisition of NKR‐P1B at comparable levels to bona fide NKR‐P1B+ NK cells. A fraction of NKR‐P1B−Ly49s3− cells remained negative for NKR‐P1B, both in vitro and after adoptive transfer in vivo. Most NKR‐P1B−Ly49s3− cells expressed the transcription factor Eomesodermin and NK cell markers, indicating that these cells represent conventional NK cells. Our findings suggest that the NKR‐P1B−Ly49s3− NK cells are precursors to NKR‐P1B single‐positive cells and that functional competence is acquired upon expression of NKR‐P1B.

• Sudworth, Amanda; Dai, Kezheng; Vaage, John T. & Kveberg, Lise (2016). Degranulation Response in Cytotoxic Rat Lymphocytes Measured with a Novel CD107a Antibody. Frontiers in Immunology. 7(572). doi: 10.3389/fimmu.2016.00572. Fulltekst i vitenarkiv Vis sammendrag

  Measuring degranulation through CD107a expression has become an advantageous tool for testing the functional capacity of cytotoxic cells. Such functional studies have been hampered in the rat by the lack of a suitable anti-rat CD107a antibody. In this study, we report a novel hybridoma generated by immunizing Armenian inbred hamsters with transfected Chinese hamster ovary cells expressing CD107a. The SIM1 clone exhibited specific reactivity with CD107a and measured degranulation from natural killer (NK) cells stimulated with target cells or mAb crosslinking of their activating receptors. Degranulation in IL-2-activated NK cells could also be measured, when using low effector to target ratios. SIM1 also stained activated CD8, but not CD4 T cells. This report characterizes the degranulation response in cytotoxic rat cells with a new antibody against rat CD107a.

• Leibelt, S; Friede, ME; Rohe, C; Gütle, D; Rutkowski, E & Weigert, A [Vis alle 10 forfattere av denne artikkelen] (2015). Dedicated immunosensing of the mouse intestinal epithelium facilitated by a pair of genetically coupled lectin-like receptors. Mucosal Immunology. ISSN 1933-0219. 8(2), s. 232–242. doi: 10.1038/mi.2014.60. Fulltekst i vitenarkiv
• Todros-Dawda, Izabela Malgorzata; Kveberg, Lise; Vaage, John Torgils & Inngjerdingen, Marit (2014). The tetraspanin CD53 modulates responses from activating NK cell receptors, promoting LFA-1 activation and dampening NK cell effector functions. PLOS ONE. 9(5). doi: 10.1371/journal.pone.0097844. Fulltekst i vitenarkiv
• Smelt, Maaike J; Faas, Marijke M.; Haan, Bart J. de; Haan, Aalzen de; Vaage, John Torgils & Vos, Paul de (2014). The Role of Alloresponsive Ly49+ NK Cells in Rat Islet Allograft Failure in the Presence and Absence of Cytomegalovirus. Cell Transplantation. ISSN 0963-6897. 23(11), s. 1381–1394. doi: 10.3727/096368913X670930. Fulltekst i vitenarkiv
• Kveberg, Lise; Sudworth, Amanda; Todros-Dawda, Izabela Malgorzata; Inngjerdingen, Marit & Vaage, John Torgils (2014). Functional characterization of a conserved pair of NKR-P1 receptors expressed by NK cells and T lymphocytes in liver and gut. European Journal of Immunology. ISSN 0014-2980. 45(2), s. 501–512. doi: 10.1002/eji.201444710. Fulltekst i vitenarkiv
• Zinöcker, Severin; Wang, Mengyu; Rolstad, Bent & Vaage, John Torgils (2012). Mesenchymal Stromal Cells Fail to Alleviate Experimental Graft-Versus-Host Disease in Rats Transplanted with Major Histocompatibility Complex-Mismatched Bone Marrow. Scandinavian Journal of Immunology. ISSN 0300-9475. 76(5), s. 464–470. doi: 10.1111/j.1365-3083.2012.02758.x. Fulltekst i vitenarkiv Vis sammendrag

  Mesenchymal stromal cells (MSC) can be used to treat graft‐versus‐host disease (GVHD) caused by allogeneic stem cell transplantation (allo‐SCT). The effectiveness of this therapy has been variable in clinical trials and in experimental animal models. In this study, we investigated the ability of bone marrow (BM)‐derived MSC to alleviate GVHD in an experimental rat model of allo‐SCT using two different combinations of major histocompatibility complex (MHC) mismatch with survival as the primary endpoint. Recipient rats received total body irradiation and a transplant of T cell‐depleted donor BM cells with either a full [PVG.7B → BN] or a partial MHC mismatch [PVG.1U → PVG.R23] restricted to the class II and non‐classical class I sub‐regions (RT1‐B/D‐CE/N/M). GVHD was invoked by infusion of graded doses of donor leukocytes 2 weeks after allo‐SCT. Weekly doses of MSC were injected starting on the day of donor leukocyte infusion. No significant overall improvement of mortality and morbidity was observed in the two transplantation settings. Stimulation of MSC with exogenous tumor necrosis factor α and interferon (IFN)γ prior to infusion could not rescue BM‐transplanted rats from lethal acute GVHD. In conclusion, repeated administrations of MSC failed to alleviate GVHD after fully or partially MHC‐mismatched allo‐SCT in the rat.

• Daws, Michael Rory; Dai, Kezheng; Zinöcker, Severin; Naper, Christian; Kveberg, Lise & Hedrich, Hans J [Vis alle 8 forfattere av denne artikkelen] (2012). Identification of an MHC Class I Ligand for the Single Member of a Killer Cell Lectin-like Receptor Family, KLRH1. Journal of Immunology. ISSN 0022-1767. 189(11), s. 5178–5184. doi: 10.4049/jimmunol.1201983. Fulltekst i vitenarkiv Vis sammendrag

  Natural killer cells are able to recognize and kill target cells according to differences in MHC class I expression. In rodents, the Ly49 receptors are primarily responsible for this MHC differentiation. We previously described the cloning of a novel C-type lectin–like receptor, KLRH1, encoded in the NK complex adjacent to the Ly49 genes and expressed by subsets of NK and NKT cells. MHC influence on selection of KLRH1+ NK cells in congenic strains suggested that KLRH1 may have an MHC ligand, although we were unable to identify any such ligand. In this study, we have used a sensitive reporter system and Fc fusion protein to demonstrate that KLRH1 binds specifically to the classical MHC class I molecule RT1-A2 of the RT1n haplotype. Cytolytic activity of KLRH1-transfected RNK-16 cells was also inhibited by target cells expressing RT1-A2n. Thus, KLRH1 represents a novel family of MHC allele–specific inhibitory receptors expressed by NK cells.

• Inngjerdingen, Marit; Kveberg, Lise & Vaage, John Torgils (2012). A Novel NKR-P1B(bright) NK Cell Subset Expresses an Activated CD25(+)CX(3)CR1(+)CD62L(-)CD11b(-)CD27(-) Phenotype and Is Prevalent in Blood, Liver, and Gut-Associated Lymphoid Organs of Rats. Journal of Immunology. ISSN 0022-1767. 188(6), s. 2499–2508. doi: 10.4049/jimmunol.1003939. Fulltekst i vitenarkiv
• Zinöcker, Severin & Vaage, John Torgils (2012). Rat mesenchymal stromal cells inhibit T cell proliferation but not cytokine production through inducible nitric oxide synthase. Frontiers in Immunology. 3. doi: 10.3389/fimmu.2012.00062. Fulltekst i vitenarkiv Vis sammendrag

  Mesenchymal stromal cells (MSC) have important immunomodulatory properties, they inhibit T lymphocyte allo-activation and have been used to treat graft-versus-host disease. How MSC exert their immunosuppressive functions is not completely understood but species specific mechanisms have been implicated. In this study we have investigated the mechanisms for rat MSC mediated inhibition of T lymphocyte proliferation and secretion of inflammatory cytokines in response to allogeneic and mitogenic stimuli in vitro. MSC inhibited the proliferation of T cells in allogeneic mixed lymphocyte reactions and in response to mitogen with similar efficacy. The anti-proliferative effect was mediated by the induced expression of nitric oxide (NO) synthase and production of NO by MSC. This pathway was required and sufficient to fully suppress lymphocyte proliferation and depended on proximity of MSC and target cells. Expression of inducible NO synthase by MSC was induced through synergistic stimulation with tumor necrosis factor α and interferon γ secreted by activated lymphocytes. Conversely, MSC had a pronounced inhibitory effect on the secretion of these cytokines by T cells which did not depend on NO synthase activity or cell contact, but was partially reversed by addition of the cyclooxygenase (COX) inhibitor indomethacin. In conclusion, rat MSC use different mechanisms to inhibit proliferative and inflammatory responses of activated T cells. While proliferation is suppressed by production of NO, cytokine secretion appears to be impaired at least in part by COX-dependent production of prostaglandin E2.

• Zinöcker, Severin; Wang, Mengyu; Gaustad, Peter; Kvalheim, Gunnar; Rolstad, Bent & Vaage, John Torgils (2011). Mycoplasma Contamination Revisited: Mesenchymal Stromal Cells Harboring Mycoplasma hyorhinis Potently Inhibit Lymphocyte Proliferation In Vitro. PLOS ONE. 6(1). doi: 10.1371/journal.pone.0016005. Fulltekst i vitenarkiv Vis sammendrag

  Background Mesenchymal stromal cells (MSC) have important immunomodulatory effects that can be exploited in the clinical setting, e.g. in patients suffering from graft-versus-host disease after allogeneic stem cell transplantation. In an experimental animal model, cultures of rat T lymphocytes were stimulated in vitro either with the mitogen Concanavalin A or with irradiated allogeneic cells in mixed lymphocyte reactions, the latter to simulate allo-immunogenic activation of transplanted T cells in vivo. This study investigated the inhibitory effects of rat bone marrow-derived MSC subsequently found to be infected with a common mycoplasma species (Mycoplasma hyorhinis) on T cell activation in vitro and experimental graft-versus-host disease in vivo. Principal Findings We found that M. hyorhinis infection increased the anti-proliferative effect of MSC dramatically, as measured by both radiometric and fluorimetric methods. Inhibition could not be explained solely by the well-known ability of mycoplasmas to degrade tritiated thymidine, but likely was the result of rapid dissemination of M. hyorhinis in the lymphocyte culture. Conclusions This study demonstrates the potent inhibitory effect exerted by M. hyorhinis in standard lymphocyte proliferation assays in vitro. MSC are efficient vectors of mycoplasma infection, emphasizing the importance of monitoring cell cultures for contamination.

• Fossum, Sigbjørn; Sæther, Per Christian; Vaage, John Torgils; Daws, Michael Rory & Dissen, Erik (2011). Paired opposing leukocyte receptors recognizing rapidly evolving ligands are subject to homogenization of their ligand binding domains. Immunogenetics. ISSN 0093-7711. 63(12), s. 809–820. doi: 10.1007/s00251-011-0553-5. Fulltekst i vitenarkiv
• Kveberg, Lise; Dai, Kezheng; Inngjerdingen, Marit; Brooks, Colin G.; Fossum, Sigbjørn & Vaage, John Torgils (2011). Phylogenetic and functional conservation of the NKR-P1F and NKR-P1G receptors in rat and mouse. Immunogenetics. ISSN 0093-7711. 63(7), s. 429–436. doi: 10.1007/s00251-011-0520-1. Fulltekst i vitenarkiv
• Inngjerdingen, Marit; Kveberg, Lise; Naper, Christian & Vaage, John Torgils (2011). Natural killer cell subsets in man and rodents. Tissue Antigens. ISSN 0001-2815. 78(2), s. 81–88. doi: 10.1111/j.1399-0039.2011.01714.x. Fulltekst i vitenarkiv
• Shegarfi, Hamid; Dai, Kezheng; Daws, Michael Rory; Ryan, James C.; Vaage, John Torgils & Rolstad, Bent [Vis alle 7 forfattere av denne artikkelen] (2011). The rat NK cell receptors Ly49s4 and Ly49i4 recognize nonclassical MHC-I molecules on Listeria monocytogenes-infected macrophages. Journal of Leukocyte Biology. ISSN 0741-5400. 89(4), s. 617–623. doi: 10.1189/jlb.1010593. Fulltekst i vitenarkiv
• Naper, Christian; Kveberg, Lise; Engh, Espen; Nestvold, Janne M.; Rolstad, Bent & Vaage, John Torgils (2010). Partial NK cell tolerance induced by radioresistant host cells in rats transplanted with MHC-mismatched bone marrow. International Immunology. ISSN 0953-8178. 22(12), s. 973–980. doi: 10.1093/intimm/dxq452. Fulltekst i vitenarkiv
• Kveberg, Lise; Jiminèz-Royo, Pilar; Naper, Christian; Rolstad, Bent; Butcher, Geoffrey W & Vaage, John Torgils [Vis alle 7 forfattere av denne artikkelen] (2010). Two complementary rat NK cell subsets, Ly49s3(+) and NKR-P1B(+), differ in phenotypic characteristics and responsiveness to cytokines. Journal of Leukocyte Biology. ISSN 0741-5400. 88(1), s. 87–93. doi: 10.1189/jlb.0110039. Fulltekst i vitenarkiv
• Shegarfi, Hamid; Dai, Kezheng; Inngjerdingen, Marit; Ryan, James C.; Vaage, John Torgils & Rolstad, Bent [Vis alle 7 forfattere av denne artikkelen] (2010). The activating rat Ly49s5 receptor responds to increased levels of MHC class Ib molecules on Listeria monocytogenes-infected enteric epithelial cells. European Journal of Immunology. ISSN 0014-2980. 40(12), s. 3535–3543. doi: 10.1002/eji.201040651. Fulltekst i vitenarkiv
• Kveberg, Lise; Dai, Kezheng; Westgaard, Ingunn Hagen; Daws, Michael Rory; Fossum, Sigbjørn & Naper, Christian [Vis alle 7 forfattere av denne artikkelen] (2009). Two major groups of rat NKR-P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding. European Journal of Immunology. ISSN 0014-2980. 39(2), s. 541–551. doi: 10.1002/eji.200838891. Fulltekst i vitenarkiv
• Nestvold, Janne M.; Omdal, Bente Kahrs; Dai, K-Z; Martens, A; Benestad, Haakon Breien & Vaage, John Torgils [Vis alle 7 forfattere av denne artikkelen] (2008). A second prophylactic MHC-mismatched bone marrow transplantation protects against rat acute myeloid leukemia (BNML) without lethal graft-versus-host disease. Transplantation. ISSN 0041-1337. 85(1), s. 102–111. doi: 10.1097/01.tp.0000296856.53493.1f. Fulltekst i vitenarkiv
• Kveberg, Lise; Dai, Kezheng; Dissen, Erik; Ryan, James C.; Rolstad, Bent & Vaage, John Torgils [Vis alle 7 forfattere av denne artikkelen] (2006). Strain-dependent expression of four structurally related rat Ly49 receptors; correlation with NK gene complex haplotype and NK alloreactivity. Immunogenetics. ISSN 0093-7711. 58(11), s. 905–916. Fulltekst i vitenarkiv
• Nylenna, Øyvind; Naper, Christian; Vaage, John Torgils; Woon, P.Y.; Gauguier, D & Dissen, Erik [Vis alle 8 forfattere av denne artikkelen] (2005). The genes and gene organization of the Ly49 region of the rat natural killer cell gene complex. European Journal of Immunology. ISSN 0014-2980. 35. Fulltekst i vitenarkiv
• Naper, Christian; Dai, Kezheng; Kveberg, Lise; Rolstad, Bent; Niemi, EC & Vaage, John Torgils [Vis alle 7 forfattere av denne artikkelen] (2005). Two structurally related rat Ly49 receptors with opposing functions (Ly49 stimulatory receptor 5 and Ly49 inhibitory receptor 5) recognize nonclassical MHC class Ib-encoded target ligands. Journal of Immunology. ISSN 0022-1767. 174. Fulltekst i vitenarkiv
• Nejad, S; Bryceson, Yenan T.; Dissen, Erik; Sundvold-Gjerstad, V; Naper, Christian & Rolstad, Bent [Vis alle 8 forfattere av denne artikkelen] (2004). cDNA cloning of a rat orthologue of SH2D2A encoding T-cell-specific adaptor protein (TSAd): expression in T and NK cells. Immunogenetics. ISSN 0093-7711. 56(5), s. 338–342. doi: 10.1007/s00251-004-0695-9. Fulltekst i vitenarkiv Vis sammendrag

  The T-cell-specific adapter protein (TSAd), encoded by the SH2D2A gene, has been implicated in modulation of proximal signaling events as well as in transcriptional regulation in human T cells. We have isolated its rat homologue (rSH2D2A) from an NK cell cDNA library and mapped the corresponding gene to chromosome 2 with a hamster-rat radiation hybrid cell panel. rSH2D2A encodes a 376 amino acid protein (rTSAd) which shows greater homology to mouse than human TSAd. In rats, rTSAd was specifically expressed by NK cells and T cells but not by other leukocytes tested. Similarly, in humans we observed abundant transcripts for TSAd in NK cells and T cells. The data suggest that TSAd may have a regulatory role in cellular activation of T and NK cells.

• Helgeland, Lars; Dissen, Erik; Dai, Kezheng; Midtvedt, Tore; Brandtzæg, Per & Vaage, John Torgils (2004). Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut. European Journal of Immunology. ISSN 0014-2980. 34, s. 3389–3400. doi: 10.1002/eji.200425122. Fulltekst i vitenarkiv Vis sammendrag

  Two populations of CD8+ IEL generally express restricted, but apparently random and nonoverlapping TCR repertoires. Previous studies in mice suggested that this could be explained by a dual origin of CD8+ IEL, i.e. that CD8ab+ IEL derive from a few peripheral CD8+ T cell lymphoblasts stimulated by microbial antigens in gut-associated lymphoid tissue, whereas CD8aa+ IEL descend from an inefficient intestinal maturation pathway.We show here that the gut mucosa, instead, becomes seeded with surprisingly broad and generally nonoverlapping CD8 IEL repertoires and that oligoclonality is induced locally after microbial colonization. In germ-free (GF) rats, both CD8ab+ and CD8aa+ IEL displayed surprisingly diverse TCR Vb repertoires, although b-chain diversity tended to be somewhat restricted in the CD8aa+ subset. CDR3 length displays in individual Vb-Cb and Vb-Jb combinations generally revealed polyclonal distributions over 6&#8211;11 different lengths, similar to CD8+ lymph node T cells, and CDR3b sequencing provided further documentation of repertoire diversity. By contrast, in ex-GF rats colonized with normal commensal microflora, both CD8ab+ and CD8aa+ IEL displayed oligoclonal CDR3 length distributions for most of the Vb genes analyzed. Our data suggest that microbial colonization induces apparently random clonal expansions of CD8ab+ and CD8aa+ IEL locally in the gut.

• Westgaard, Ingunn Hagen; Berg, Siri F.; Vaage, John Torgils; Wang, Lawrence L; Yokoyama, Wayne M. & Dissen, Erik [Vis alle 7 forfattere av denne artikkelen] (2004). Rat NKp46 activates natural killer cell cytotoxicity and is associated with Fc{epsilon}RI{gamma} and CD3{zeta}. Journal of Leukocyte Biology. ISSN 0741-5400. 76, s. 1200–1206. doi: 10.1189/jlb.0903428. Fulltekst i vitenarkiv Vis sammendrag

  NKp46 has been identified in the human, rat, mouse, monkey, and cattle. We have generated a monoclonal antibody, WEN23, against rat NKp46. By flow cytometry, NKp46 is expressed by all natural killer (NK) cells but not by T cells, B cells, granulocytes, monocytes, dendritic cells, or macrophages. Thus, NKp46/WEN23 is the first NK cell-specific marker in the rat. In a redirected lysis assay, preincubation of the effector cells with WEN23 augmented lysis of the Fc receptor (FcR)+ murine tumor target cells, indicating that NKp46 is an activating NK cell receptor. Moreover, preincubation of the effector cells with WEN23 F(ab')2 fragments reduced killing of target cells, confirming the activating function of NKp46 and indicating that the mouse tumor target cells express a ligand for rat NKp46. Lysis of FcR- mouse and human tumor target cells was reduced after incubation of effector cells with WEN23, suggesting that rat NKp46 recognizes a ligand that is conserved between primates and rodents. By Western blot and immunoprecipitation using WEN23, NKp46 is expressed as a monomer of ~47 kDa in interleukin-2-activated NK cells. The immunoreceptor tyrosine-based activation motif bearing adaptor proteins CD3{zeta} and the {gamma} chain of FcRI for IgE (Fc{epsilon}RI{gamma}) with NKp46 from lysates of NK cells, indicating that rat NKp46 activates NK cell cytotoxicity by similar pathways as CD16.

• Naper, Christian; Hayashi, Shigenari; Kveberg, Lise; Niemi, Eréne C.; Lanier, Lewis L. & Vaage, John Torgils [Vis alle 7 forfattere av denne artikkelen] (2002). Ly-49s3 is a promiscuous activating rat NK cell receptor for nonclassical MHC class I-encoded target ligands. Journal of Immunology. ISSN 0022-1767. 169, s. 22–30. Fulltekst i vitenarkiv
• Naper, Christian; Hayashi, Shigenari; Joly, Etienne; Butcher, Geoffrey W; Rolstad, Bent & Vaage, John Torgils [Vis alle 7 forfattere av denne artikkelen] (2002). Ly49i2 is an inhibitory rat natural killer cell receptor for an MHC class Ia molecule (RT1-A1c). European Journal of Immunology. ISSN 0014-2980. 32, s. 2031–2036. Fulltekst i vitenarkiv
• Naper, Christian; Hayashi, Shigenari; Løvik, Guro; Kveberg, Lise; Niemi, Eréne C. & Rolstad, Bent [Vis alle 9 forfattere av denne artikkelen] (2002). Characterization of a novel killer cell lectin-like receptor (KLRH1) expressed by alloreactive rat NK cells. Journal of Immunology. ISSN 0022-1767. s. 5147–5154. Fulltekst i vitenarkiv
• Torgersen, Knut Martin; Vaage, John Torgils; Rolstad, Bent & Tasken, Kjetil (2001). A soluble LAT deletion mutant inhibits T-cell activation: reduced recruitment of signalling molecules to glycolipid-enriched microdomains. Cell Signal. 13, s. 213–220. Fulltekst i vitenarkiv
• Rolstad, Bent; Naper, Christian; Løvik, Guro; Vaage, John Torgils; Ryan, James C. & Kirsch, Ralph D. [Vis alle 8 forfattere av denne artikkelen] (2001). Rat natural killer cell receptor systems and recognition of MHC class I molecules. Immunological Reviews. ISSN 0105-2896. 181, s. 149–157. Fulltekst i vitenarkiv
• Løvik, Guro; Vaage, John Torgils; Rolstad, Bent & Naper, Christian (2001). The effect of in vivo depletion of NKR-P1+ or CD8+ lymphocytes on the acute rejection of allogeneic lymphocytes (ALC) in the rat. Scandinavian Journal of Immunology. ISSN 0300-9475. 54, s. 341–347. Fulltekst i vitenarkiv
• Løvik, Guro; Vaage, John Torgils; Dissen, Erik; Szpirer, Claude; Ryan, James C. & Rolstad, Bent (2000). Characterization and molecular cloning of rat C1qRp, a receptor on NK cells. European Journal of Immunology. ISSN 0014-2980. 30, s. 3355–3362. Fulltekst i vitenarkiv
• Leong, Louise Y. W.; Rolle, Anne-France Le; Deverson, Edward V.; Powis, Simon J.; Larkins, Audrey P. & Vaage, John Torgils [Vis alle 11 forfattere av denne artikkelen] (1999). RT1-U: Identification of a novel, active, class Ib alloantigen of the rat MHC. Journal of Immunology. ISSN 0022-1767. 162, s. 743–752. Fulltekst i vitenarkiv
• Naper, Christian; Ryan, James C.; Kirsch, R.; Butcher, Geoffrey W; Rolstad, Bent & Vaage, John Torgils (1999). Genes in two major histocompatibility complex class I regions control selection, phenotype, and function of a rat Ly-49 natural killer cell subset. European Journal of Immunology. ISSN 0014-2980. 29, s. 2046–2053. Fulltekst i vitenarkiv

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• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Vis alle 30 forfattere av denne artikkelen] (2023). A novel non-invasive FcRn-targeted mucosal vaccine strategy. Fulltekst i vitenarkiv
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Vis alle 30 forfattere av denne artikkelen] (2023). A non-invasive subunit vaccine technology targeting FcRn induces protective mucosal and systemic antibody immunity in mouse models. Fulltekst i vitenarkiv
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Vis alle 30 forfattere av denne artikkelen] (2023). A novel non-invasive FcRn-targeted mucosal vaccine strategy. Fulltekst i vitenarkiv
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Vis alle 40 forfattere av denne artikkelen] (2023). Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7). npj Vaccines. 8(1). doi: 10.1038/s41541-023-00600-6. Fulltekst i vitenarkiv
• Anthi, Aina Karen; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa; Tjärnhage, Elias & Lode, Heidrun Elisabeth [Vis alle 29 forfattere av denne artikkelen] (2023). A non-invasive subunit vaccine technology targeting FcRn induces protective mucosal and systemic antibody immunity in mouse models. Fulltekst i vitenarkiv
• Rasmussen, Tilde; König, Marton; Lorentzen, Åslaug Rudjord; Schikora-Rustad, Stine; Berge, Tone & Holmøy, Trygve [Vis alle 17 forfattere av denne artikkelen] (2022). Safety of a third SARS CoV 2 mRNA vaccine dose in people with multiple sclerosis. Fulltekst i vitenarkiv
• König, Marton; Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; Chopra, Adity; Tran, Trung & Torgauten, Hilde Marie [Vis alle 28 forfattere av denne artikkelen] (2022). Immunogenicity and efficacy of mRNA-COVID-19 vaccines in people with multiple sclerosis. Fulltekst i vitenarkiv
• Nissen-Meyer, Lise Sofie Haug; Hervig, Tor Audun; Fevang, Børre; Norheim, Gunnstein; Kran, Anne-Marte Bakken & Vaage, John T. [Vis alle 7 forfattere av denne artikkelen] (2022). Covid-19-rekonvalesensplasma fra norske blodgivere. 142(9), s. 768–770. doi: 10.4045/tidsskr.22.0057. Fulltekst i vitenarkiv
• Midtvedt, Karsten; Vaage, John T.; Heldal, Kristian; Munthe, Ludvig Andre; Lund-Johansen, Fridtjof & Åsberg, Anders (2022). Fourth dose of the SARS-CoV-2 vaccine in kidney transplant recipients with previously impaired humoral antibody response. American Journal of Transplantation. ISSN 1600-6135. doi: 10.1111/ajt.17091. Fulltekst i vitenarkiv
• König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, The Trung; Schikora-Rustad, Stine & Vaage, Eline Benno [Vis alle 22 forfattere av denne artikkelen] (2021). Humoral Immunity to SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis using High-Efficacy Disease Modifying Therapies. Fulltekst i vitenarkiv
• Szodoray, Peter; Nakken, Britt; Osnes, Liv T. N.; Naper, Christian; Vaage, John Torgils & Egeland, Torstein (2012). IMMUNE REGULATORY EFFECTS OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN AUTOIMMUNE DISEASES. Cytometry. ISSN 0196-4763. 82B(6), s. 379–380. Fulltekst i vitenarkiv
• Zinöcker, Severin & Vaage, John Torgils (2011). Rat bone marrow-derived mesenchymal stromal cells suppress T cell activation by production of nitric oxide. Fulltekst i vitenarkiv
• Zinöcker, Severin & Vaage, John Torgils (2011). Rat Bone Marrow Stromal Cells Suppress T Cell Activation by Production of Nitric Oxide. Scandinavian Journal of Immunology. ISSN 0300-9475. 73(4), s. 379–379. Fulltekst i vitenarkiv
• Kvalheim, Gunnar; Wang, Mengyu; Zinöcker, Severin; Camilio, Ketil Andre; Rolstad, Bent & Vaage, John T. [Vis alle 7 forfattere av denne artikkelen] (2010). Remission and tumor cell protection in PVG rats by subcutaneous injection of LTX-315 into an aggressive malignant rat mesenchymal tumor with stemness characteristics. Fulltekst i vitenarkiv Vis sammendrag

  Background: LTX-315 (Oncopore) is a chemically designed cationic nonapeptide derived from a natural host defensive CAP, bovine lactoferricin (LfcinB) in development for local treatment of tumours. Earlier studies have demonstrated that treatment of A20 lymphomas and CT26WT carcinomas with LTX-315 in immunocompetent mice resulted in tumour regression. Re-challenge with tumor cells in the cured animals showed that a long- term protection was induced against the tumor. Methods: In the current experiments we have investigated if LTX-315 also can have the same effect on a novel established malignant rat mesenchymal tumor cell line with “stemness” properties. Following long term culturing of bone marrow derived rat mesenchymal cells we developed a rat transformed mesenchymal cell line (rTMSC). Previously we have shown that s.c. as well as i.v. and i.p. injection of rTMSC form immature sarcoma tumors both in nude rats as well as in PVG rats. The rTMSC has been stabled marked with a dual reporter gene GFP and Leuciferase and in the current study CCD camera was used for dynamic living imaging. 5×105 rTMSCs were subcutaneously inoculated into 20 PVG rats. After 7 days measurable tumors could be observed and 18 animals was treated with LTX-315. Results: In spite of repeated injection with the peptide 8 animals lost tumor control, while 9 animals within 38 days achieved complete tumor responses as assessed with CCD camera. Re-challenges of the tumor free animals with injection of 5×104 tRMSCs show no tumor growth while all control animals had a fast tumor formation. Conclusions: 50% of the treated animals have developed an impressive tumor protection of this aggressive mesenchymal tumor with “stemness” properties. Most likely more animals can be cured if the peptide injection procedure can be improved and further studies are underway. Altogether our results bear promises for LTX-315 in future cancer therapy. No significant financial relationships to disclose. © 2010 by American Society of Clinical Oncology

• Zinöcker, Severin; Wang, Mengyu; Gaustad, Peter; Kvalheim, Gunnar; Rolstad, Bent & Vaage, John Torgils (2010). Mesenchymal Stem Cell Therapy for Graft-versus-Host Disease. Fulltekst i vitenarkiv
• Kveberg, Lise; Dai, Kezheng; Martinsen, Stine; Fossum, Sigbjørn & Vaage, John Torgils (2009). Phylogenetic and functional conservation of the NKR-P1G NK receptor in rat and mouse. Fulltekst i vitenarkiv
• Kveberg, Lise; Fossum, Sigbjørn & Vaage, John Torgils (2009). Phylogenetic and functional conservation of the NKR-P1G receptor in rat and mouse. Fulltekst i vitenarkiv
• Zinöcker, Severin; Wang, Mengyu; Kvalheim, Gunnar; Nestvold, Janne M.; Rolstad, Bent & Vaage, John Torgils (2009). Mesenchymal Stromal Cells effectively suppress T cell alloreactivity in vitro but not Graft-versus-Host Disease in Rats. Fulltekst i vitenarkiv
• Zinöcker, Severin; Nestvold, Janne M.; Wang, Mengyu; Kvalheim, Gunnar; Vaage, John Torgils & Rolstad, Bent (2007). Mesenchymal Stem Cells as a treatment for Graft-vs-Host Disease. Fulltekst i vitenarkiv
• Kveberg, Lise; Westgaard, Ingunn Hagen; Dai, Kezheng; Daws, Michael Rory; Fossum, Sigbjørn & Naper, Christian [Vis alle 7 forfattere av denne artikkelen] (2007). The NKR-P1 family of receptors in rat recognizes C-type lectin related molecules. Fulltekst i vitenarkiv
• Kveberg, Lise; Westgaard, Ingunn Hagen; Dai, Kezheng; Daws, Michael Rory; Fossum, Sigbjørn & Naper, Christian [Vis alle 7 forfattere av denne artikkelen] (2007). The NKR-P1 family of receptors in rat recognizes C-type lectin-related molecules. Fulltekst i vitenarkiv
• Zinöcker, Severin; Nestvold, Janne M.; Wang, Mengyu; Kvalheim, Gunnar; Vaage, John Torgils & Rolstad, Bent (2007). Mesenchymal Stem Cell Therapy in a Rat Model for GvHD. Fulltekst i vitenarkiv
• Zinöcker, Severin; Dai, Kezheng; Naper, Christian; Daws, Michael Rory; Rolstad, Bent & Vaage, John Torgils (2007). A novel reporter system to identify NK receptor-MHC ligand interactions. Fulltekst i vitenarkiv
• Inngjerdingen, Marit; Kveberg, Lise; Naper, Christian; Dai, Kezheng; Rolstad, Bent & Vaage, John Torgils (2007). Functional characterization of two major NK cell subsets in the rat, a Ly49+ and a NKR-P1C+ subset. Fulltekst i vitenarkiv
• Sollid, Ludvig Magne; Vaage, JT & Vaage, John Torgils (2006). Cross-dressing T cells go wild. Nature Medicine. ISSN 1078-8956. 12, s. 611–612. Fulltekst i vitenarkiv
• Torgersen, Knut Martin; Vang, Torkel; Vaage, John Torgils; Ryan, James C.; Rolstad, Bent & Tasken, Kjetil (1999). Molecular events in the regulation of T and NK cell signalling. Fulltekst i vitenarkiv
• Tunheim, Gro; Kran, Anne-Marte Bakken; Rø, Gunnar Øyvind Isaksson; Hungnes, Olav; Lund-Johansen, Fridtjof & Vaage, Eline Benno [Vis alle 9 forfattere av denne artikkelen] (2021). Seroprevalence of SARS-CoV-2 in the Norwegian population measured in residual sera collected in January 2021. Norwegian Institute of Public Health, Division of Infection Control and Environmental Health. ISSN 9788284061825. Fulltekst i vitenarkiv Vis sammendrag

  Norsk sammendrag Covid-19 er en infeksjonssykdom som skyldes det nye koronaviruset SARS-CoV-2. Infeksjon med SARS-CoV-2 induserer antistoffer mot viruset, og funn av virusspesifikke antistoffer i blodprøver fra uvaksinerte indikerer gjennomgått infeksjon. Dette er den tredje studien som måler antistoffer mot SARS-CoV-2 i serumprøver som er systematisk samlet inn fra ulike geografiske områder i Norge, og som representerer alle aldersgrupper. Den første studien, basert på restsera samlet inn i april/mai 2020 og august 2019, ble publisert som en rapport i juni 2020 (1). Den andre studien, basert på restsera samlet inn på sensommeren 2020, ble publisert som en rapport i desember 2020 (2). I denne studien, ble til sammen 1912 restsera samlet inn i løpet av januar 2021 (uke 53-6) fra 17 laboratorier. De fleste prøvene (85,7 %) ble samlet inn mellom uke 1-3. Serumprøvene ble testet for antistoffer mot SARS-CoV-2 med en metode som er utviklet og etablert ved Avdeling for immunologi og transfusjonsmedisin ved Oslo universitetssykehus. Ut ifra disse målingene lå den estimerte andelen av den norske befolkningen som har antistoffer mot SARS-CoV-2 (seroprevalensen) på 3,2 % (95 % kredibilitetsintervall 2,3 – 4,1) i denne perioden. Dette er høyere enn den estimerte seroprevalensen sensommeren 2020 (0,6 % (95 % kredibilitetsintervall 0,2 – 1,2)) (2). Antistoffer mot SARS-CoV-2 ble funnet i totalt 61 prøver. De positive prøvene var fra personer bosatt i 10 av de 11 norske fylkene, men det var ingen signifikante forskjeller i estimert seroprevalens mellom de ulike fylkene. Imidlertid var det stor variasjon i antall prøver fra hvert fylke. Det ble ikke funnet noen signifikante forskjeller i estimert seroprevalens mellom ulike aldersgrupper eller mellom ulike kjønn.

• Tunheim, Gro; Kran, Anne-Marte Bakken; Rø, Gunnar Øyvind Isaksson; Hungnes, Olav; Lund-Johansen, Fridtjof & Tran, Trung [Vis alle 8 forfattere av denne artikkelen] (2020). Seroprevalence of SARS-CoV-2 in the Norwegian population measured in residual sera collected in late summer 2020. Folkehelseinstituttet. ISSN 9788284061559. Fulltekst i vitenarkiv Vis sammendrag

  COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2. Infection with SARS-CoV-2 induces antibodies to the virus, therefore the presence of these antibodies in a person’s blood indicates that the person has been infected with SARS-CoV-2. This is the second study measuring antibodies against SARS-CoV-2 in residual serum samples collected systematically from various geographical regions in Norway and covering all age groups. The first study with residual sera from April/May 2020 and August 2019, was published as a report in June 2020 (1). In the present study, a total of 1812 residual sera were sampled from 16 microbiology laboratories from late July to mid-September 2020 (week numbers 30-37). The sera were tested for antibodies against SARS-CoV-2 using a novel in-house assay established at the Department of Immunology, Oslo University Hospital. Based on these measurements, the estimated seroprevalence in the Norwegian population in the late summer was 0.6% [95% credible interval (CrI) 0.2 - 1.2]. This is not significantly different from the seroprevalence estimate based on the 900 samples collected in the spring (1.0% [95% CrI 0.1- 2.4])(1). Antibodies against SARS-CoV-2 were found in samples from 6 of the 11 counties, but there were no significant differences between the seroprevalence estimates for each county. However, the sample size from each county varied considerably (from 20 to 387) and the number of positive samples were limited (11 in total). There were no significant differences between the seroprevalence estimates for the various age groups or between males and females. During the summer of 2020, the pandemic was quite contained in Norway. This may explain why the estimated seroprevalence for the Norwegian population was similar in the spring and in the late summer. In this first follow-up study, more laboratories contributed, and a greater number of samples was tested, leading to better precision of the seroprevalence estimate. New follow-up studies of antibodies against SARS-CoV-2 in future collections of residual sera will provide further information about the development of the COVID-19 pandemic in Norway

• Tunheim, Gro; Kran, Anne-Marte Bakken; Rø, Gunnar Øyvind Isaksson; Steens, Anneke; Hungnes, Olav & Lund-Johansen, Fridtjof [Vis alle 9 forfattere av denne artikkelen] (2020). Seroprevalence of SARS-CoV-2 in the Norwegian population measured in residual sera collected in April/May 2020 and August 2019. Folkehelseinstituttet. ISSN 9788284061092. Fulltekst i vitenarkiv Vis sammendrag

  COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2. Infection with SARS-CoV-2 induces antibodies to the virus, therefore the presence of these antibodies in a person’s blood indicates that the person has been infected with SARS-CoV-2. This is the first study measuring antibodies against SARS-CoV-2 in serum samples collected systematically from various geographical regions in Norway and covering all age groups. A total of 900 residual sera from nine laboratories were sampled in week numbers 17-20, 2020, and tested for antibodies against SARS-CoV-2 using a novel in-house assay established at the Department of Immunology, Oslo University Hospital. Based on these measurements, the estimated seroprevalence in the Norwegian population is probably close to 1% (1.0% (95% credible interval 0.1% - 2.4%)). We did not find any differences in seroprevalence by gender or age group. However, there seem to be geographical differences in the prevalence of seropositive individuals; there was a non-significant trend indicating that the number of positive samples and the estimated seroprevalence was higher in Oslo than in other regions. However, the sample size was limited as not all counties were included, and only an average number of 100 samples have been collected from each laboratory. Therefore, these results should be interpreted with caution. Follow-up studies of antibodies against SARS-CoV-2 in future collections of residual sera can provide further information about the development of the COVID-19 pandemic in Norway.

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