Can You Get By With Only One Covid Shot?

Sam Fazeli, a Bloomberg Opinion contributor who covers the pharmaceutical industry for Bloomberg Intelligence, answered questions about the wisdom of changing protocols for Covid-19 vaccine dosage as experts in the U.S. and elsewhere weigh tweaks to speed up inoculations ahead of any spread by variants. The conversation has been edited and condensed.

Both the Pfizer Inc.-BioNTech SE and Moderna Inc. vaccines follow two-shot regimens. But research is now showing that one shot may be enough for people previously infected with Covid. Is this true?

This question has been on people’s minds for a while now: Namely, is it possible that a prior infection with Sars-Cov-2 acts like the first dose of the vaccine? The latest data shows that it might. But we have to be very careful before jumping to conclusions and changing vaccination protocols. While research from two different groups shows that the immune response to one shot of the vaccine, measured by antibody levels, is much stronger in people who have been previously infected, it doesn’t answer the question of whether this is enough to provide a similar efficacy in preventing disease. Moreover, we still don’t know what the best immune “biomarker” — usually called an immune correlate — for disease prevention is. Are high antibody levels enough to give you high efficacy, or do you need the other parts of the immune system, too? And does the immune reaction work just as well in the elderly as in younger people? All these things need to be studied in a clinical trial.

Does the severity of infection come into play when recommending whether or not a person needs only one shot? In other words, is this only relevant for people who came down with Covid-19 or also those who were infected with the virus but were asymptomatic?

The short answer is we don’t know yet. But having said that, there is data showing that those who clear the virus and only have mild symptoms of Covid-19 have a different type of immune response — involving more activation of the cellular arm of the immune system — than those who have more severe disease. So the effect of a dose of vaccine may also vary in these two groups.

Don’t antibodies in people who had Covid fall over time? So one shot might not do the trick for people who had the disease a while ago, right?

Possibly, but there are other things involved as well. In most people who have been infected, you would expect some immune memory to have been formed. The vaccine dose then “awakens” this memory, kicking the system into overdrive and creating an antibody response. What we don’t know is whether the immune reaction to the vaccine is actually targeting the version of the virus that is represented in the vaccine or just replaying the immunity to the prior infection. This is called “original antigenic sin” and it’s a complex issue. Given the emergence of variants and the chances that future vaccines may be designed to target these new forms of the virus, rather than the ones that were dominant in earlier days of the pandemic, we need to study this further so we can be sure that Covid sufferers’ immune memory triggers the right response after a vaccination, whether one or two doses.

There is also some talk of getting first shots out to as many as possible, and if necessary, delaying the timing of the second shot – even for those who were never infected. Is this wise?

This is a very thorny subject. The argument of, “Don’t let perfect get in the way of good” could apply here, but without hard data it is taking a risk. Updated clinical trial data from those who received the vaccine developed by AstraZeneca Plc with the University of Oxford suggests that a single shot followed by another three months later may induce better protection than two shots taken closer together. But we have absolutely no idea how this would work with other vaccines. The Pfizer-BioNTech and Moderna shots, which use new mRNA technology, have been found to work well when the shots are given 21 and 28 days apart, respectively. While these are some of the shortest intervals between a prime and booster dose used in vaccinations, we don't know if they would be just as effective if that timing was stretched out. It’s possible that efficacy after just one dose could fall faster for these mRNA vaccines compared with Astra’s, which uses different technology. Age may also be a factor. There is some research showing that 50% of those older than 80 did not respond to one dose of the Pfizer-BioNTech vaccine, though they all responded well after the second dose. This suggests we should not experiment with longer dosing intervals for the mRNA vaccines, at least in older subjects.

How do the variants fit into this whole question of dosage and vaccinations?

This takes us back to the idea of “original antigenic sin.” It’s possible that future vaccinations designed to attack new variants may be less effective than those used to protect against the original form of the virus. It’s as if the immune system gets stuck in a “groove” and keeps making antibodies to the older version of the virus even when vaccinated against a new version. This needs to be studied very quickly so we know what the risk is, not only to those who were previously vaccinated but also those who are vaccinated after a previous infection.

How long do these vaccines seem to last?

We have very little data on that. I expect to hear updates in the next few months.

Even as experts debate one shot instead of two, there are recommendations out now about masking, saying two is better than one. What’s the story?

This is quite straightforward. No barrier is 100% protective. To be 100% proof it needs to basically block the transfer of air – which would kill you. So if using one mask with one layer gives you x% protection, using two layers gives you xx%. If a variant of the virus is more transmittable, i.e. you need fewer viral particles to get an infection, then it stands to reason that wearing two masks gives you better protection.  

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Bloomberg Opinion provides commentary on business, economics, politics, technology and markets.

©2021 Bloomberg L.P.

BQ Install

Bloomberg Quint

Add BloombergQuint App to Home screen.