Booster vaccinations are assumed to trigger stereotypical re-expansions of memory B cells (Bmem). In a SARS-CoV-2 prime-boost cohort, however, the magnitude of the secondary response was not predicted by preboost Bmem frequencies, but was inversely associated with pre-existing specific antibody levels, pointing to antibody feedback as the dominant limiting parameter.
ABSTRACT
Clonal expansion of memory lymphocytes after each antigen encounter is the primary mechanism for amplifying immunity. For most vaccines, boosters are common practice and are expected to stimulate proliferation of pre-existing memory B cells (Bmem), thereby expanding the antigen-specific Bmem pool, along with driving their differentiation into antibody-producing plasma cells that replenish antibody titers. It is widely assumed that the number of Bmem present in the body prior to administration of a booster vaccination will define the magnitude of the ensuing response. By comparing Bmem frequencies and antibody titers in the same individuals after primary and secondary vaccination with SARS-CoV-2 Spike (S-antigen)-encoding mRNA, we found that expansion of Bmem and the relative increase of the secondary antibody response were not determined by the number of Bmem measured before the second vaccine inoculation. Instead, both were inversely correlated with levels of S-antigen-specific serum IgG prior to the secondary antigen exposure. Collectively, these data suggest that secondary B cell responses are constrained by antibody feedback inhibition of Bmem, rather than their scarcity.