Natural infection and vaccination together provide maximum protection against COVID variants

A combination of vaccination and naturally acquired infection appears to boost the production of maximally potent antibodies against the COVID-19 virus, new UCLA research finds.

The findings, published today in the peer-reviewed journal mBio, raise the possibility that vaccine boosters may be equally effective in improving antibodies’ ability to target multiple variants of the virus, including the delta variant, which is now the predominant strain, and the recently detected omicron variant. (The study was conducted prior to the emergence of delta and omicron, but Dr. Otto Yang, the study’s senior author, said the results could potentially apply to those and other new variants.)

“The main message from our research is that someone who has had COVID and then gets vaccinated develops not only a boost in antibody amount, but also improved antibody quality — enhancing the ability of antibodies to act against variants,” said Yang, a professor of medicine in the division of infectious diseases and of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. “This suggests that having repeated exposures to the spike protein allows the immune system to continue improving the antibodies if someone had COVID then been vaccinated.”

(The spike protein is the part of the virus that binds to cells, resulting in infection.)

Yang said it is not yet known whether the same benefits would be realized for people who have repeated vaccinations but who have not contracted COVID-19.

The researchers compared blood antibodies in 15 vaccinated people who had not been previously infected with SARS-CoV-2, the virus that causes COVID-19, with infection-induced antibodies in 10 people who were recently infected with SARS-CoV-2 but not yet vaccinated. Several months later, the 10 participants in the latter group were vaccinated, and the researchers then reanalyzed their antibodies.  Most people in both of the groups had received the Pfizer–BioNTech or Moderna two-dose vaccines.

The scientists evaluated how antibodies acted against a panel of spike proteins with various common mutations in the receptor-binding domain, which is the target for antibodies that help neutralize the virus by blocking it from binding to cells.

They found that the receptor-binding domain mutations reduced the potency of antibodies acquired both by either natural infection or vaccination alone, to about the same degree in both groups of people. When previously infected people were vaccinated about a year after natural infection, however, their antibodies’ potency was maximized to a point that they recognized all of the COVID-19 variants the scientists tested.

“Overall, our findings raise the possibility that resistance of SARS-CoV-2 variants to antibodies can be overcome by driving further maturation through continued antigenic exposure by vaccination, even if the vaccine does not deliver variant sequences,” the researchers write. They suggest that repeated vaccinations may have the capacity to accomplish the same thing as getting vaccinated after having had COVID-19, although further research will be required to address that possibility.

The study’s other authors are F. Javier Ibarrondo, Christian Hofmann, Ayub Ali, Paul Ayoub and Dr. Donald Kohn, all of UCLA.

The study was funded by the AIDS Healthcare Foundation and various private donors.