More than 20 COVID vaccines are in use globally, each one based on the ancestral coronavirus SARS-CoV-2 that surfaced in Wuhan, China, over two years ago. Among them, mRNA vaccines are believed to offer the best protection against severe disease.
"It's been clear for quite a while that none of them is as good as the mRNA vaccines that dominate the U.S. landscape," says Nathaniel Landau, a virologist at NYU Langone Health in New York, referring to the Pfizer and Moderna shots.
But a new preprint study shows that other vaccines can be as effective as mRNA shots when given to people who've had a prior SARs-CoV-2 infection.
For these individuals "it doesn't matter which vaccine they get," says Theodora Hatziiouannou, a virologist at The Rockefeller University in New York who helped lead the study. "They will likely be protected against [reinfection from] all the current variants."
During the study, scientists collected blood samples from 197 fully-immunized people in Mexico, where five types of COVID vaccines have been deployed so far. Roughly half these individuals were infected prior to vaccination, and the researchers had records of which type of shot they were each given.
Then the team measured how well immune cells and the molecules they produce in those blood samples could recognize and bind to portions of the SARS-CoV-2 virus — specifically its spike proteins. Spike proteins jut from SARS-CoV-2 like studs on a tire and hook onto human cell receptors to initiate an infection. When the immune components are able to bind to these proteins and block them, the virus is unable to enter a cell and is therefore unable to replicate.
The researchers tested the immune response to spike proteins from the ancestral coronavirus as well from newer variants, including omicron BA.1. The newer omicron BA.2 variant had only recently surfaced when the study began and was not evaluated
To compare how well the vaccines worked to prevent viral spike proteins from binding to cells, the team zeroed in on two of the immune system's key components.
First, are neutralizing antibodies — they provide a frontline defense that deflect spikes from their human cell target.
Second are antibody-producing B cells that provide long-term reinforcements. These cells retain a memory of the virus' spike protein and can rapidly generate new and even better antibodies against it long after the front-line neutralizing antibodies have waned.
Analyzing the blood samples revealed two sets of results. In people who hadn't yet been infected with SARs-CoV-2, mRNA shots elicited the best anti-viral responses from antibodies and memory B cells. But the strength of those responses dwindled a bit more with each successive variant of the virus. And while mRNA retained a consistent lead against the variants, neither the mRNA shots nor the other vaccines could mount appreciable responses to prevent infection by omicron — although according to Moore, other immune components called T cells can provide added protection from severe disease. T cells were not measured in the study.
In people who had been infected with SARs-CoV-2 and were then vaccinated, the outcome was completely different: All the vaccines provided a major immunological boost against re-infection, and the differences between the mRNA shots and the other ones "began to blur," says John Moore, a virologist at Weill Cornell Medicine in New York who was not involved in the study.
Of the five vaccines tested, four produced nearly identical immune reactions. This group included Pfizer's mRNA shot as well a shot made by AstraZeneca, the Sputnik V shot made by the Gamaleya Research Institute of Epidemiology and Microbiology in Russia, and one from Cansino, a Chinese company. A fifth vaccine, CoronaVac, made by Sinovac Biotech in China, was the worst performer, though still protective to some degree.
These vaccines work in different ways. Pfizer's mRNA is a lab-created molecule that teaches cells to recognize and respond to future infections. AstraZeneca's vaccine, as well as the Sputnik V and Cansino shots, also deliver genetic instructions for responding to the spike proteins of SARS-CoV-2 but in a harmless cold virus.
The Sinovac vaccine, meanwhile, is made of killed SARs-CoV-2 particles.
Paul Bieniasz, a virologist at The Rockefeller University and a corresponding author on the paper, says Pfizer's mRNA shot performs best among uninfected people because it exposes the immune system to more spike protein than the other vaccines and in a form that neutralizing antibodies can more easily bind to.
But why do the different vaccines perform comparably after an infection? Bieniasz says the explanation lies in how memory B cells prepare for a future viral attack. After an infection, the cells go through a training process (called affinity maturation) that teaches them how to generate better antibodies against SARS-CoV-2 – ones that bind more tightly, not only to the variant that they were first introduced to but also future variants the immune has never seen before. After a previously infected person is vaccinated, "those [trained] B cells spring into action," Bieniasz says.
The study's point that vaccinating after a case of COVID provides protection against future infections is supported by a newly-published Israeli study. Researchers found that unvaccinated individuals who had recovered from COVID and were then given the Pfizer vaccine had significantly lowered reinfection risks after getting a Pfizer vaccine.
Summing up the two findings, Moore says "The Israeli paper tells you that vaccinating convalescent people has real-world benefits and the Rockefeller paper tells you the vaccine you use [either mRNA or non-mRNA] is inconsequential — you get the benefits from each."
Furthermore, "a single vaccine dose was sufficient to confer benefit [in the Israeli study]," Moore says, which suggests that among people who have already been infected, the standard two-dose regime is not necessary. Halving the two-shot regimen for previously infected people "would save a lot of doses and hence needs to be seriously considered," Moore says.
Evidence that non-mRNA vaccines are powerfully protective for the vast numbers of people with prior infections is welcome news, especially in countries where those shots have been widely adopted. "People are going to wind up having similar immunity by various routes," Bieniasz says. And these other vaccines have a lot to contribute to how they accumulate that immunity."
Charlie Schmidt is an award-winning freelance science writer based in Portland, Maine. His work has appeared in Scientific American, Undark, the Atlantic, Science Magazine, Nature and The Washington Post.
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