Doctor holding Coronavirus vaccine. COVID 19 concept
Credit: Paul Biris/Getty Images

A new study has uncovered more details about memory B cell responses to SARS-CoV-2, the virus that causes COVID-19, after recovery from natural infection or post-vaccination. The study, coauthored by David Fear, from King’s College London, is published in Viral Immunology. 

Many research studies have found that serological SARS-CoV-2-specific IgG antibody titers wane over time, yet, it is unclear whether these changes reflect potential reactivation of antigen-specific memory B cell populations.

These researchers write that, “This is especially true in the contexts of differing COVID-19 disease severity and after vaccination regimens. This study aimed to investigate these by polyclonal in vitro reactivation of MBC populations followed by analysis using SARS-CoV-2 antigen-specific B cell ELISpots and IgG antibody ELISAs.”

Immunity to SARS-CoV-2 infection, from either natural exposure or vaccination, occurs from classical adaptive immunity, where the production of neutralizing antibodies by B cells attacks the infection and confers protection against subsequent re-exposure. This long-term protection is considered immunological memory.

Antigen-specific B cell responses to SARS-CoV-2, the authors write, “are predominantly mounted against regions within the Nucleocapsid (N) and Spike (S) protein antigens.” They add that, “The evaluation of serological memory in numerous studies has shown both disease severity-associated differences in circulating antigen-specific antibody titers, as well as waning of N and S protein-specific antibodies over time after both disease resolution and vaccination.”

Other studies of N- and S-specific memory B cells have shown the maintenance or an increase in these populations after either the resolution of infection or after vaccination with the BNT162b2 mRNA COVID-19 vaccine.

In one part of this study, the scientists used donor blood from 52 individuals, including health care professionals. at high risk of SARS-CoV-2 exposure. The samples came from Guy’s and St Thomas’ NHS Foundation Trust (GSTT) and Valentine Health Partnership as well as from patients within GSTT. Donors included healthy controls with no signs of COVID-19, asymptomatic cases, mild/moderate symptoms with negative serology, mild/moderate symptoms with positive serology, and severe COVID-19 disease, which was confirmed by PCR.

For the vaccine part of the study, 14 individuals with no known prior SARS-CoV-2 infection were recruited. Samples were taken before vaccination and/or at 1 and 6 months post-vaccination with a second dose of BNT162b2.

Results showed that among those recovered from natural infection, COVID-19 serologically-positive donors had strong antigen-specific memory B cell-associated responses. Post-vaccination, donors showed robust serological antigen-specific antibody responses against spike protein that waned over time. Memory B cell-associated responses against spike protein were also observed, but showed less waning over time.

Comparison between groups of serological N and S protein-specific IgG antibodies in donor plasma at 1 month of convalescence showed significantly higher N protein-specific IgG in both the severe group, relative to both healthy control and negative groups, and the positive group relative to both healthy control and negative groups.

“This study is of particular relevance at the moment, because with millions vaccinated, previously infected, or both, studies such as this one may tell us how long we might expect the immunity to last,” says Rodney S. Russell, PhD, Editor-in-Chief of Viral Immunology, from Memorial University of Newfoundland, St. John’s.

Understanding this process is also critical to guide development of new vaccines, including those that are more protective for cancer patients, who are at particularly high risk of death from COVID-19. Such patients can have an inadequate immune response to vaccination, according to recent research from Mayo Clinic Cancer Center.

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