Researchers compared peripheral blood mononuclear cells in people with high and low antibody titers after two doses of the Pfizer/BioNTech (BNT162b2) mRNA vaccine. They found a positive correlation between naïve B cells present before vaccination and high antibody titers.
Among the several vaccines being administered to combat COVID-19, one among them, the BNT162b2 mRNA vaccine, has been reported to reduce disease severity. However, with the pandemic still continuing around the world, several new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative pathogen of COVID-19 – have emerged. Some of these variants are highly transmissible and have even exhibited partial resistance to immune responses elicited through vaccines or prior infections.
Although BNT162b2 has been shown to elicit neutralizing antibodies against the different variants, it may be important to improve these vaccines before the virus acquires more resistant mutations that can render the current models ineffective.
The levels of antibodies produced after vaccination could provide useful and important information to develop better vaccines and optimize vaccination strategies. Age has been shown to be associated with lower antibody response. Even among the young population, there are people with very low antibody levels without any known factors for reduced antibody titers.
Correlation of antibody levels to B cells
To understand why some people have low antibody levels, researchers from Chiba University and Chiba University Hospital in Japan investigated the characteristics of peripheral blood mononuclear cells (PBMCs) before and after vaccination with the BNT162b2 vaccine. The team recently released their findings on the bioRxiv* preprint server, while their article undergoes peer review.
The team chose 20 individuals with low antibody levels after two doses of the vaccine and compared them to 20 individuals who had a high antibody titer, about 10 times more than the levels of the low titer group.
When the authors determined the frequency of CD4+ and CD8+ T cells, B cells, and monocytes in the PBMCs, they found a positive correlation between the B cells and high antibody titers. Surprisingly, there was no association between the antibody titers and the CD4+ T cells, although the role of these cells is very well known in antibody response. There was also no correlation between antibody concentrations and intermediate monocytes. This suggests that the abundance of B cells is associated with a robust antibody response after BNT162b2 vaccination.
They also found a positive correlation between increased frequency of activated CD8+ T cells after vaccination and high antibody levels, indicating strong T cell responses are associated with a high antibody response.
Naïve B cells important
Previously, analysis of human naïve B cells (B cells that have never been exposed to an antigen) has shown that some naïve antibodies can bind to and neutralize SARS-CoV-2. This suggests an abundance of naïve B cells may produce a good antibody response, which is consistent with previous findings that young people have higher antibody titers as they are believed to have more naïve B cells. More studies are needed to understand this relationship better.
However, previous studies that have examined B cell fractions have not found any correlation between naïve B cells and antibodies in influenza vaccination. The difference between the effect of the two vaccines could be because of the presence of influenza virus-specific memory B cells from previous infections or vaccination. It is also likely that immune responses to mRNA vaccines may be different from those to inactivated virus vaccines. Further studies on mRNA vaccines can provide more insights into vaccine development.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.