This text was first published in Norwegian at Medisinbloggen. Read the Norwegian text here.
Vaccines were the key to coming out of the last corona pandemic in a good way. Many people have talked about how much we learned about vaccines during the pandemic. For me, however, the answer is: less than we could have hoped for.
We knew a lot about coronaviruses before the pandemic
Before the coronavirus pandemic, researchers had investigated the structure of various coronaviruses [1, 2] and identified the spike proteins on the virus surface as a good target for vaccine development. Vaccines had been developed against both SARS-CoV-1 (which had a small outbreak in Asia in 2003) and MERS (which has been regularly infecting people in the Middle East since 2012). In fact, clinical trials of vaccines against these coronaviruses had also been conducted [3, 4].
In addition, there had been a number of clinical trials with vaccines based on DNA or mRNA against various viruses[5, 6], so we had available vaccine technologies that allowed us to quickly produce new vaccines.
So, when SARS-CoV-2 came along we had the necessary knowledge of vaccine technologies and coronaviruses to quickly develop good and effective vaccines. All we really needed was the gene sequence of the spike for this particular virus variant.
What did the corona pandemic teach us about vaccine development?
Although much was known, there was also much that was unknown. How good would the protection from the vaccines be? We didn't know the specific efficacy against SARS-CoV-2 until it was tested in phase 3 clinical trials. Fortunately, the efficacy was very good [7, 8]. As the SARS-CoV-2 virus mutated and changed further, the effect against infection disappeared, but the protection against severe disease has fortunately been good and long-lasting.
What we learned about vaccine development during the pandemic was that using the spike in an mRNA vaccine could actually provide around 95% protection against being infected by the virus variant that was in the vaccine [7, 8]. The new vaccines were also a big boost for mRNA vaccine technology since this was the first time mRNA vaccines were used on a large scale.
Furthermore, we learned a lot about different forms of vaccine production, efficient approval procedures, as well as distribution to different countries. This is important.
Which virus will cause the next pandemic?
We live in a world where we are getting closer and closer to viruses and bacteria through travel and urbanization. Viruses are found in all forms of living things, both plants and animals. While plant viruses pose little threat to us, there is no telling what may come from mammals or birds in the future.
International monitoring of viruses in mammals, birds and humans is ongoing, but it is still not possible to get a full overview of what is latent in the environment around us.
It is very difficult to predict which type of virus is most likely to cause a new pandemic in the future. In other words, which viruses can change so that they can spread between people. We simply have to be prepared for dealing with the unknown.
In the future, we will need a lot of basic research
We don't know what will hit us during the next pandemic. The only thing that is certain is that the next pandemic will not be caused by SARS-CoV-2. On the other hand, it will probably be a virus we know as little about as we did at the start of the pandemic, or even less.
We therefore need to learn more about different viruses. But we also need to know which type of immune response provides the best protection against the different viruses. The less we know about the family of the next virus that comes along, the more difficult it will be to create good vaccines against it.
We need basic research that provides knowledge about:
- the interaction between different viruses and our immune system
- what characterizes good and protective responses in different parts of the population
- how we can use the vaccines we have as effectively as possible for the common good
- how we can slow down the spread in an appropriate way
What type of vaccines will be best against the next pandemic?
Vaccines come in many forms. During the corona pandemic, we received approval for the first time to use both mRNA and DNA vaccines in different population groups. That's super cool! In addition, vaccines were created that consisted of proteins or the entire virus.
All these vaccine types have advantages and disadvantages. Vaccines based on proteins, mRNA and DNA can be made quickly, but require you to know exactly which part of the virus you want an immune response against. Vaccines with the whole virus can in some cases provide a broader type of immune response. This can be beneficial for fighting the virus, but can also have undesirable side effects.
Going forward, it is important that we do even more research into the strengths and weaknesses of the various vaccine types, so that we can choose the type that is best suited for dealing with the particular situation we find ourselves in.
We need a more holistic perspective on pandemics
A pandemic can affect all parts of society. Consequently, it's important to consider pandemic management in a holistic context, not just based on the effective rollout of vaccines.
Then we can start with the geographical factor. Viruses do not spread unless they are actually present. In other words, areas of the country with no proven virus do not need the same strategies as areas where there is actually a virus. In other words, it makes sense to plan differential handling for different parts of Norway. As a starting point, we believe that it is the most densely populated areas that will have the highest risk of infection and disease, and it therefore makes sense to plan future management from this perspective.
In addition, the risk of serious illness and death will probably be different for different population groups. Thus, we need to think about how much we are willing to shut down society in the future to protect the most vulnerable individuals. Where do we set the threshold for when a virus represents a danger that is great enough to justify considering invasive measures to control the spread of infection?
It is difficult to come up with an answer to these questions, as the answer will often be subjective. We should therefore have a discussion that puts us in a better position to assess the pros and cons next time. The time for such a discussion is now, before we once again have an imminent known pandemic danger.
We have an interdisciplinary focus on pandemic management
At the Center for Pandemics and One-Health Research (P1H), our research is aiming to shed light on how we can best prepare for the next pandemic.
One example is how we can plan the roll-out of vaccines with different degrees of protection as efficiently as possible. Will the purpose of the vaccine be to protect against infection or severe disease?
If you manage to protect the people who are particularly vulnerable to severe illness, the actual spread of infection becomes less important. Especially if you consider that many of the viruses we may face in the future can change at least as quickly as SARS-CoV-2, and that vaccine-based protection against infection will therefore also require frequent updated doses against the virus that is circulating. Is it worth it?
So, the first question that should be answered is what type of protection we need a particular vaccine to provide. It is also important to keep in mind that the effect of vaccines will vary in the population, and that the elderly often do not get the full benefit of vaccination right away.
Future pandemic management requires an interdisciplinary approach. Immunological, virological and epidemiological knowledge should be combined with, among other things, law, social sciences, psychology and the humanities. In this post, I've focused a lot on vaccines, but the effective use of vaccines also requires an understanding of the social context in which they will be used.
During the pandemic, we experienced a high level of trust in vaccines, the authorities and handling in the population in Norway. However, a lot of nonsense about vaccines and their consequences is still being spread on social media.
It should be noted here that side effects will occur with all vaccines, which we also saw with the various vaccines against SARS-CoV-2. Sometimes it is difficult to distinguish side effects caused by the vaccine from other things, while other times it is not difficult at all.
We must bear in mind that the ongoing discussion in social media may affect what opportunities we have going forward. Will trust be intact when dealing with the next pandemic? The answer to this question will affect the room we have available for manoeuvring when dealing with the next pandemic.
References
1. Kirchdoerfer, R.N., et al., Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis. Sci Rep, 2018. 8(1): p. 15701.
2. Yuan, Y., et al., Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun, 2017. 8: p. 15092.
3. Martin, J.E., et al., A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine, 2008. 26(50): p. 6338-43.
4. Modjarrad, K., et al., Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis, 2019. 19(9): p. 1013-1022.
5. Alberer, M., et al., Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet, 2017. 390(10101): p. 1511-1520.
6. Bahl, K., et al., Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses. Mol Ther, 2017. 25(6): p. 1316-1327.
7. Baden, L.R., et al., Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med, 2021. 384(5): p. 403-416.
8. Polack, F.P., et al., Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med, 2020. 383(27): p. 2603-2615.