Read on Twitter
I received this email from someone last week that I can't stop thinking about. I probably received this since I have been openly optimistic about vaccine efforts. So I wanted to explain exactly why I am glass half-full.
Many of the grim posts about predicted efficacy (only 50%) have used the flu vaccine as a comparison. But as with many aspects of the pandemic (e.g. IFR, transmission), flu is not a very informative prior for vaccines without some major adjustments.
To be considered effective, the flu vaccine has to protect against symptomatic disease by *any* flu strain, whether it is in the vaccine or not. There are usually at least 4 circulating flu strains and sometimes the vaccine doesn't match one or more strains. That's a big ask...
In contrast, there is not much question as to what strain we should vaccinate against for SARS-CoV-2. The genetic diversity is really low. The neutralizing antibody targets are also much simpler than for other viruses like RSV or HIV. https://www.pnas.org/content/117/38/23652
So let's adjust flu as a prior and focus on just one strain. Against the 2009 H1N1 strain, the efficacy was 73%, measured by reduction in incidence of symptomatic disease. But based on the immunology, that could be a baseline, not a ceiling https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(16)00129-8.pdf
The flu vaccine most widely used in the US violates many of the rules we have learned about what it takes to make a durable, high level response. It is detergent split, it has no adjuvant, and unsurprisingly, protection often doesn't last that long. https://science.sciencemag.org/content/370/6513/237.long
To me it is remarkable that the flu vaccine works as well as it does. In contrast, the Novavax COVID vaccine for example meets many rules we think are important. And encouragingly, the early responses are substantially better than from natural infection https://www.nejm.org/doi/full/10.1056/NEJMoa2026920
This excess is particularly good because you usually take a loss as antibodies squeeze through from the blood into the upper respiratory tract (not as much of an issue for the lungs). So there is at least the possibility of getting sterilizing immunity in some.
In this regard, vaccine efficacy is seen as a yes or no--did it prevent disease or not? Useful for objective FDA approval, but immunity is a spectrum--what could have been severe disease becomes mild; viral shedding reduces from 6 days to 2. https://www.sciencedirect.com/science/article/pii/S0264410X99003345?via%3Dihub
For all of these reasons, I have been bullish about likely efficacy of several of the vaccines (no conflicts). Caveat: I am often (my lab says usually) wrong. Of course there are manufacturing and distribution issues, and we need to let the trials play out to look at safety...
But I don't think I am alone amongst immunologists in my optimism. I'll close it out with this beautiful op-ed by @VirusesImmunity and @RMedzhitov, two of the real leaders in our field: https://www.nytimes.com/2020/07/31/opinion/coronavirus-antibodies-immunity.html
