The reasearch group has several ongoing projects on HIV and Tuberculosis.
The research group focus on studies of immune pathogenesis in HIV infection and immunological biomarkers that can identify HIV patients at risk of poor reconstitution of the immune system despite effective anti-viral therapy (ART) as well as co-morbidities related to chronic immune activation. Studies are performed on prospectively collected biobank from HIV patients at the Dep. of Infectious Diseases, OUH and in collaboration with national and international partners.
We have in recent years conducted several clinical phase I/II interventional trials with therapeutic HIV vaccines (Vacc-4x and Vacc-C5), with potential to serve as a key component of a possible cure for HIV (funded by the Research Council of Norway, RCN, and in cooperation with Bionor Pharma and Eurocine Vaccines) and we are planning for new HIV vaccine studies. We have completed a pilot study of the therapeutic potential of probiotics in HIV patients (partnership with TINE AS) and a phase I/II intervention study with probiotics is ongoing (see below). We have established a HIV quality register and provide data to international multicenter HIV cohort studies (Cascade, EuroSIDA). The group is a member of the Nordic HIV Cure consortium where we in joint projects will contribute with clinical data and biobank material from various HIV cohorts.
ONGOING HIV STUDIES
- Immune regulation and regulatory T cells in HIV: Suppression of HIV-specific T cells by HIV antigens in chronic infection
Increased activity of T regulatory cells (Treg) inhibits adequate immune responses in chronic HIV infection. We study Treg function and characteristics through in vitro analysis of biobank material from HIV patients in order to discover mechanisms of regulation of immune responses and to identify possible therapeutic points of attack. Project leaders are Kvale and Taskén in collaboration with Dyrhol-Riise and postdoctor Berg Lorvik. The study is funded by the South-Eastern Norway Regional Health Authority (HSØ).
- New quantitative assays testing functional suppressive capacity of effector T cells in relation to interventions with antiretroviral therapy and immune modulation
A dysfunctional immune system may explain why some HIV patients experience rapid disease progression and poor immune responses to vaccines. This project has identified mechanisms for regulation of immune responses through functional analysis of immune cells from HIV patients and developed methods for measuring this "inhibitory regulation". We have found heterogenicity of T cell regulation mediated by the cytokines IL-10, TGF-β and the co-stimulatory molecule PD-1 in untreated HIV infection. The chemokine MIP-1β may serve as a potential biomarker for lack of immunological response to ART. Project leader is Kvale in cooperation with Dyrhol-Riise. PhD student Prebensen. The study is funded by HSØ.
- Optional immune modulating therapy and improved vaccination responses by adjuvant administration of a cyclooxygenase type 2 inhibitor in HIV-infected patients
We have previously shown that anti-inflammatory drugs with immune modulatory effects, provide a more effective immune response against both HIV and various T cell dependent vaccines. We have conducted a clinical intervention study in HIV patients treated with the cyclooxygenase-2 inhibitor etoricoxib. The clinical study was completed in 2014 and data show a positive immune modulatory effect after four months of treatment with etoricoxib in untreated HIV patients. Whether this treatment strategy is useful in patients on ART is still uncertain and analysis of collected material are ongoing. Project leader Kvale in collaboration with Dyrhol-Riise and Taskén. The study has been funded by RCN.
- HIV-infected patients with immune-virological discordance in response to ART: Studies of Viral dynamics, Immune activation, and Microbial translocation
In HIV infection 15% of patients do not respond with adequate reconstitution of the immune system despite prolonged and effective ART (immunological non-responders = INR) and the reasons are not clear. Through studies of human biobank collected from our HIV patients we have found that INR patients have more inflammation with higher levels of the chemokine IP-10 as well as activated Treg and effector T cells in the blood compared with patients with normal CD4 counts. Intervention with probiotics given to INR patients reduced inflammatory markers in blood. There is ongoing in-depth analysis of the innate and adaptive immune system to study the mechanisms in more detail. Project leader Dyrhol-Riise in collaboration with Trøseid, Kvale and Taskén. PhD student Stiksrud. The study is funded by the University of Oslo and Oslo University Hospital.
- Adjuvant mucosal therapy in HIV-infected men with insufficient response to antiretroviral therapy
One of the reasons why the immune system is not fully restored in well treated HIV infection can be reduced mucosal barrier of the gut with leakage of bacterial products that activates the immune system in an unfavorable manner. The project builds on our previous studies of INR patients. We recruit HIV-infected INR patients to a Phase I/II clinical intervention study including colon biopsies where they receive a probiotic supplement for eight weeks in addition to ART (OUSHIVProbiot2, ClinicalTrials.gov NCT02640625). We will examine whether probiotics can serve as an adjunctive therapy in INR patients with a dysfunctional intestinal mucosa. Project leader Reikvam in collaboration with Dyrhol-Riise, Kvale and Medhus (Dep. of Gastroenterology OUH, Ullevål). PhD student Meyer-Myklestad. The study is funded by the K.G. Jebsen Inflammation Research Center and HSØ.
Read more about the study
The research group focus on studies of immune pathogenesis in tuberculosis (TB) and immunological biomarkers that can identify TB patients at risk of developing disease from latent stages and show efficacy of treatment. Studies are performed in collaboration with national and international partners on human biobank material prospectively collected from TB patients admitted at the Dep. of Infectious Diseases, OUH before and during treatment. We have established a TB quality register and contribute with data to international multicenter studies initiated by the European TB network (TBnet). We have joined a European-African network with focus on clinical trials of host-directed therapy in TB. From 2016 we are partner in a RCN (GLOBVAC) study in Tanzania in collaboration with Statens Serum Institute (SSI) in Copenhagen and the University of Bergen. We have also recently established a partnership with the Immunology Research Group at the University of Stellenbosch, South Africa, a leading institution in TB research.
ONGOING TUBERCULOSIS STUDIES
- New diagnostic and prognostic biomarkers-a translational research approach to fight the tuberculosis epidemic
TB infected people with certain T cell and cytokine profiles in blood seem to have increased risks of developing active disease from latent stages. We have ongoing studies of immune profiles and soluble mediators in blood which can serve as potential prognostic or diagnostic biomarkers as well as measure treatment effectiveness. We have shown that functional T cell signatures correlate to early treatment responses in TB. The chemokine IP-10 measured by the point-of-care test Dry Plasma Spots (DPS) can serve as a biomarker of treatment responses. The study has so far resulted in two PhD degrees (Tonby and Feruglio). Project leader Dyrhol-Riise in collaboration with Kvale and Taskén.
The study is funded by the University of Oslo and Oslo University Hospital.
- Therapeutic vaccination and immune modulation - new treatment strategies for the multidrug-resistant tuberculosis pandemic. A phase I clinical trial of the therapeutic TB H56:IC31 vaccine and cyclooxygenase-inhibitors
T regulatory cells, anti-inflammatory factors (cytokines, prostaglandin E2) and cyclooxygenase (COX) protect primarily against pathological tissue damage, but may also suppress the immune system. COX-2 inhibitors have been shown to modulate the immune system in TB animal models in a favorable manner. We have in preclinical in vitro studies of human cells from TB patients demonstrated that COX inhibitors modulate Th1 effector and T regulatory cells. Thus, they may have potential as host-directed therapy in TB with special relevance for multi-resistant TB. We started in 2015 a research project in collaboration with SSI in Copenhagen where we in a mouse model study the effects of COX-2 inhibition. From 2016 we have recruited TB patients to a phase I/II clinical intervention trial to study the safety and immunogenicity of etoricoxib in combination with the TB vaccine H56:IC31. Patients are recruited from OUH, several hospitals in the Oslo region and Haukeland University hospital; Bergen (TBCOX2, ClinicalTrials.gov NCT02503839). Project leader Dyrhol-Riise in collaboration with Kvale, Taskén, postdocs Tonby and Jenum. From 2017 a PhD student will be included.
The project is funded by RCN (GLOBVAC) and the South-Eastern Norway Regional Health Authority.