Issue 26: One Shot or Two?

Feb 15, 2021

By Akiko Iwasaki, Ph.D.

Professor of Immunobiology and Molecular, Cellular, and Developmental Biology


In response to the still limited supply of COVID-19 vaccines, governments, health departments, and scientists are evaluating various ways to stretch existing doses and vaccinate more of the global population as quickly as possible. This effort is particularly urgent given the concern over SARS-CoV-2 variants that are increasingly prevalent throughout the world. In some cases, this has meant delaying the second vaccine dose. But for individuals who have already had COVID, data suggest it may be possible to forego the second dose altogether. HVP Editor Kristen Jill Abboud recently spoke with Akiko Iwasaki, Professor of Immunobiology and Molecular, Cellular, and Developmental Biology at Yale School of Medicine, about establishing effective immunity in individuals who have recovered from COVID-19.

An edited version of the conversation appears below.

What do we know about whether or not two doses of vaccine are required in people who have already been infected with SARS-CoV-2?

There are already preprint papers demonstrating that for those people who have had COVID before, one shot is probably sufficient [see Must Read below]. First of all, there is some level of antibodies against the virus to begin with in people who were already infected. Then, with one shot, they basically develop the level of antibodies that most people get with two shots of vaccine. And so, based on the antibody levels that these people can generate, I think that they really only need one dose of vaccine.

Does that indicate that the infection primed the immune system and the vaccine shot is effectively boosting those existing immune responses?

Immunologically, that is exactly what I think is going on. We know that infection generates immune responses, not just B-cell but also T-cell memory responses, and so if you’ve recovered from COVID, you will have some level of immunity. That varies between people—some people make very good antibody levels after infection and others low levels. But just one shot of vaccines appears to be boosting immune responses in all of these people to the point where they have antibody levels that are considered optimal for protection.

Is this true for those who have mild COVID cases or even asymptomatic infections?

The data from the preprints show that people who had even low levels of antibodies following natural infection are able to bring up their antibody levels with only one shot. Even if you had mild disease, although I’m not sure about asymptomatic infection, just one shot appears to be able to bring the antibody levels up high enough.

Is it possible that people who have recovered from COVID-19 might already have antibody levels that would protect them against reinfection without vaccination?

Some people will cross the threshold of antibodies needed for protection right from the get go, which, of course, would be useful to know. To determine this, we need to know the correlate of protection, which we don’t have yet. We know from animal studies in primates that neutralizing antibodies are a good correlate of protection, we just don’t know what antibody level is required for protection in humans. Hopefully these data on correlates of protection are forthcoming.

Have you heard of people who already had COVID having more pronounced reactions to the second vaccine dose?

Yes, I have. Many people have reached out to me because they are afraid to get the second shot after they had a strong reaction to the first one. I worry that with this very narrow window of time in between the first and second shots that if they are making a robust antibody response, the second shot might result in an even stronger reaction.

Given the limited vaccine supply, would it make more sense from a public health perspective to instead allocate these second doses to vaccinate more people?

That’s what I’ve been saying from the beginning. If evidence suggests that people who have had COVID develop high enough antibody levels after one shot, we could conserve that second dose and give it to people who really need it.

What about vaccine boosters to address the viral variants, against which some existing vaccines seem to be slightly less effective? Would these booster shots be advisable for people who have recovered from COVID?

Vaccine companies are currently thinking about giving a third shot in an effort to boost immune responses and address the virus variants that are circulating, which is something that will need to be considered carefully for people who have already had COVID. Perhaps it would make sense to wait four months to get the booster if their antibody levels are waning.

Interview by Kristen Jill Abboud

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