Infection Plus Vaccination for improved defense against COVID-19

Infection plus vaccination yields better antibodies against COVID-19 variants


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The pandemic continues to propagate, primarily because as the coronavirus spike, protein evolves so that it helps the virus infiltrate a host cell and new variants emerge that help the infection spread more easily from person to person. As a result, antibodies developed after an early infection or after vaccination may not be sufficient to protect the body from these newer emerging variants.

Antibodies against the SARS-CoV-2 spike protein produced by the immune system can help identify and prevent future infections. But not all antibodies are the same. People who have recovered from COVID-19 early in a pandemic or have had current vaccines may not necessarily fend off new variants.

Well, this week in mBio, an open-access journal of the American Society for Microbiology, researchers report that combining the two can produce a more potent defense.

According to the study, people who’ve had an infection and received a vaccine have high-quality antibodies that act against spike variants. It is more effective than having antibodies through one mode.

“It shows that antibody quality can improve over time, and not just quantity,” said immunologist and physician Otto Yang, M.D., at the David Geffen School of Medicine at the University of California Los Angeles. Finding the optimal mix of antibodies could help guide future preventive efforts. “It fits into understanding what the optimal vaccination regimen is,” said Yang, who led the new study.

An area of the spike protein is called the receptor binding domain, or RBD. It enables the virus to invade a host cell. This region is also a critical target for antibodies, but random mutations in the RBD mean it’s an ever-changing target.

In the new study, Yang and his colleagues compared anti-RBD antibodies in the blood of participants to the ability of the antibodies to neutralize the virus.

In uninfected patients who had received 1 of 2 COVID-19 vaccines, the researchers found antibodies that were less effective against mutations in the new variants (like Beta or Gamma) than against the original genetic sequence encoded in the vaccine.

Similarly, when the researchers analyzed blood samples from people who’d been infected with the coronavirus before May 2020—before the first confirmation of variants—they had reduced potency against newer variants compared to the original. These findings suggest that mild infection and vaccination produce antibodies that still leave a person vulnerable to new variants.

But the results differed dramatically for individuals who’d been infected before May 2020 and vaccinated a year later. In these prior-infected, vaccinated individuals, the researchers found unchanged antibodies in efficacy against the original sequence—but just as potent against new variants. Yang said those results align with similar findings by other groups, published earlier this year, showing high-quality antibodies in people who’d been infected and vaccinated.

“We might have predicted that antibodies would continue to evolve and get better with multiple exposures,” said Yang, “but we didn’t expect it to happen that fast.”

Studies like this show how antibodies change in quality could help researchers improve the implementation of vaccines and boosters—not only for COVID-19 but also for the next pathogen that comes along, said Yang.

Journal Reference

  1. F. Javier Ibarrondo, Christian Hofmann, Ayub Ali, Paul Ayoub, Donald B. Kohn and Otto O. Yang, Infection Plus Vaccination Yields Better Antibodies Against COVID-19 Variants; mBio – DOI: 10.1128/mBio.02656-21


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