What do we know about the Pfizer vaccine so far?

Christopher Gill: They talked about a 90-percent reduction in the risk of getting COVID19. So, what they are describing is an analysis based on who did or did not get infected, and therefore they are describing a preventative vaccine rather than a disease-attenuating vaccine (i.e. one that doesn’t stop you getting infected, but makes you less sick if you do). That aligns with how we expect the vaccine to work, because it targets the spike protein to prevent the virus infecting cells.

What do we not know yet?

A lot.

For example: Was there a difference in vaccine efficacy after one versus two doses? Did the vaccine’s efficacy vary by the age of the subject (maybe less effective in elderly than younger people, for example)? Did they include individuals who only had one dose of their planned two in this analysis, or was it only based on those who completed the two-dose series?

Did the vaccine induce robust levels of ACE2 neutralizing antibodies? These are the antibodies that interfere with the virus’ ability to bind to and enter a cell, and so are probably a better proxy of immunity than just antibodies against COVID-19 in general.

And, was there evidence that baseline non-specific coronavirus antibodies modified individuals’ risk of getting COVID-19, or the immune response to the vaccine? That question arises because of the theory that exposure to “common cold” coronaviruses might provide cross reactive antibodies, and perhaps this is why the disease seems less common and severe in children. I’m not very persuaded by that theory, but there is increasing evidence that it might play a role.

So, we shall see.

With the limited information, are you hopeful?

Yes. This is a moment where there is light at the end of the tunnel.

Obviously we need to know a lot more. But this vaccine is very similar to the Moderna vaccine, and the Phase I Moderna data were very promising. Their vaccine did induce neutralizing antibodies at titers quite comparable to those in individuals who had recovered from COVID-19.

Any big doubts?

I think the issue of efficacy as a function of age is critically important, and will have a major impact on how we deploy the vaccine early on.

What I mean here is that it feels just and right that our highest risk elderly should be vaccinated first, being at highest risk of severe disease. But if the vaccine does not induce robust immunity in these subjects, then vaccinating the elderly might, paradoxically, be the least effective way of protecting the elderly. In that case, we’d be better off vaccinating healthy younger adults to create firewalls against spread to the elderly.

Similarly, I’d like to know more about responses after the first dose of the two-dose series. There are logistical challenges to giving any vaccine at scale, and these are magnified if you have to give repeated doses over time.

Lastly, a huge logistical unknown is how to manage the unique cold chain requirements for the vaccine: -80°C. Most doctors’ offices don’t have a -80°C freezer, so how is this supposed to be delivered?

When a vaccine is finally developed and ready to go, what will the next challenges be?

Vaccine uptake, how long immune protection persists, the potential need for boosters over time, and long-term safety at a population level.

Also, it will be important to identify an immunologic correlate of protection. That is an immune response that can be measured that you know can substitute for clinical prevention of disease. If you know that thing that can be measured in a test tube, then you can use that correlate to bridge between different classes of COVID-19 vaccine—and there are many, many under development, and 11 in late stages of development. It may not be necessary to do 40,000-subject trials for each one if we can bridge based on a common immunologic feature that would have to be demonstrated instead of efficacy in order to achieve licensure.

And the arrival of a vaccine, or a group of vaccines, is not going to end the pandemic overnight. This will take time, and I worry that poorer countries will be forgotten when case numbers start to fall here. Zambia needs a COVID-19 vaccine as much as the US does.