A combination of vaccination and naturally acquired infection appears to provide maximum protection against the variants of SARS-CoV-2, the virus that causes COVID-19, according to a study.

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The findings, published in the journal mBio, raise the possibility that vaccine boosters may be equally effective in improving antibodies' ability to target multiple variants of the virus. "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 Otto Yang, a professor at the University of California - Los Angeles (UCLA) in the US.

"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," said Yang, the study's senior author. The spike protein is the part of the virus that helps it to enter and infect the cells.

It is not yet known whether the same benefits would be realised for people who have repeated vaccinations but who have not contracted COVID-19, the researchers said. They compared blood antibodies in 15 vaccinated people who had not been previously infected with SARS-CoV-2, with infection-induced antibodies in 10 people who were recently infected with the virus but not yet vaccinated.

Several months later, the 10 participants in the latter group were vaccinated, and the researchers then reanalysed their antibodies. Most people in both of the groups had received the Pfizer 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 neutralise 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 maximised to a point that they recognised 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 said.

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.