Special Issue 1: Interpreting the Interim Pfizer/BioNTech COVID-19 Vaccine Data

Nov 09, 2020

By Wayne Koff, Ph.D.

President & CEO

Wayne Koff is the founding President and CEO of the Human Vaccines Project (HVP). Earlier today, following Pfizer’s and BioNTech’s announcement that their mRNA-based COVID-19 vaccine candidate had an interim efficacy of more than 90%, HVP Editor Kristen Jill Abboud discussed the implications of these results with Koff. An edited version of the conversation appears below.

This special issue also includes reactions from several experts in the field and a summary of the ongoing Phase III efficacy trial, including trial demographics and next steps.

Put these results in context for us. What does this level of efficacy mean and how does it compare to the efficacy of other vaccines?

These are incredibly exciting results. It is a remarkable achievement to show these results from a large, international efficacy trial in less than a year since the identification of the virus. Having a vaccine with 90% efficacy would be similar to some of the best pediatric vaccines we have, so this is really encouraging.

There aren’t any licensed vaccines based on the mRNA platform. What are the implications for other vaccine candidates based on this platform, for SARS-CoV-2 or other pathogens?

I think this is the other key observation that has come out of this initial data. There has been tremendous promise for a long time on the potential of mRNA as a vaccine platform, but this is really the first time that this level of efficacy has been observed with an mRNA vaccine candidate. This opens the door for the potential of mRNA vaccines for other respiratory diseases, such as RSV, for which we don’t have a vaccine, or influenza, for which the annual vaccine is only around 60% effective. This also provides an opportunity to explore using mRNA for vaccines for non-communicable diseases as well, such as cancer vaccines. It is exciting news for the potential of mRNA vaccines.

Obviously, these data are only preliminary so there are many questions remaining. What are the most critical data that we should be watching for as the trial reaches its final endpoint?

As the companies have pointed out, this is an initial look at the efficacy of the vaccine. The trial will not meet its endpoint until there are 164 disease endpoints among the trial volunteers, which could come relatively quickly given the expansiveness of the pandemic. The key issue will be safety. Ensuring that the vaccine is as safe as possible is really paramount, and that will be a critical part of the Emergency Use Authorization (EUA) or licensure application. After considering safety, there are still many other questions. The demographic of the populations enrolled in the trial will be critical, and, specifically, the data among the elderly, which is the population at the highest risk of severe disease. Related to that, we will want to understand whether this vaccine protects equally well against mild and severe disease.

Another important issue, which the companies will only have data on after some time, is the durability of the vaccine-induced immune responses. Ideally, a vaccine would have life-long protective immunity. There are some licensed vaccines that work extremely well in terms of durability—smallpox and yellow fever vaccines are the examples of this. Whereas other vaccines, including those for influenza, pertussis, and mumps, are less effective in terms of durability. That is one of the questions we will have to wait to answer as vaccine trial participants are followed for a longer period of time.

Another important question is whether there are any data yet on the identification of potential correlates of protection: are neutralizing antibody titers the key assay that we need to be looking at for other vaccines? Once you have a vaccine that has shown efficacy and is made available, either through licensure or EUA, you may need to do bridging studies for other vaccines that are based on that correlate.

Is it likely that correlates can be determined after 164 infections or will more data/follow-up be required?

I think there will be a huge amount of work immediately to try to figure out the correlate. It might be that we need to have larger numbers to determine it, or we might get lucky and it may simply be the neutralizing antibody titer.

This vaccine is a two-shot regimen that must be stored at ultra-cold temperatures. How does this complicate deployment efforts?

This will certainly be an issue for delivery and deployment of this vaccine on a global scale. The ideal vaccine would be one shot and not have issues with cold chain storage. But there have been advances in cold-chain storage in recent years, as well as with the technologies associated with GPS systems and use of drones to deliver vaccines, so this ultimately will become an engineering problem.

What are the implications of this early result for the other vaccines in efficacy trials, even those that aren’t using an mRNA delivery system? Does this raise the expectations for the efficacy of other candidates as well?

If you look at the data from non-human primates and the immunogenicity data in people from Phase I trials, the levels of neutralizing antibodies are relatively similar for all the platforms. Some vaccines are inducing higher levels of neutralizing antibodies than others, but most of the leading candidates are in the same ballpark, which bodes well for all the candidates if the neutralizing antibody titer is in fact the correlate.

Prior to these preliminary results, I assumed we were going to see efficacy in the range of between 50-80% based on all the data. If it turns out that this result holds up and there is really over 90% efficacy, and if the vaccine works as well in the elderly as in young adults—two really big questions—then we will have an amazing result from this unprecedented effort.

Interview by Kristen Jill Abboud

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