Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested. Here, we examine memory B cell evolution 5 months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccines in a cohort of SARS-CoV-2 naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge 5 months after vaccination of naive individuals express antibodies that are equivalent to those that dominate the initial response. We conclude that memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines would produce a quantitative increase in plasma neutralizing activity but not the qualitative advantage against variants obtained by vaccinating convalescent individuals.

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

“…A longer dose interval was also associated with higher antibody concentrations at all time points after the second dose (all p<0.05), consistent with previous reports [24-26]. COVID-19 convalescent status was also associated with maintaining 0.26 log 10 higher antibody concentrations at three and six months following the second dose (both p<0.05), consistent with superior durability of “hybrid” immunity induced by infection followed by vaccination [27-29].…”

“…Similar to other reports [27-29], our findings indicate that individuals who have contracted COVID-19 are likely to benefit from vaccination. Compared to naïve participants, convalescent individuals displayed a slower rate of antibody decline, and multivariable analyses demonstrated that binding and neutralization activity was higher in this group at six months after the second dose.…”

“…In multivariable analyses however, a higher number of chronic health conditions emerged as the sole independent correlate of antibody decline, with each additional condition associated with a 5-day shorter half-life (p=0.017; Table 2 ). Furthermore, COVID-19 convalescent status was associated with a 14-day longer antibody half-life after adjustment for other factors (p=0.056), consistent with improved durability of hybrid immunity [27-29].…”

mRNA Vaccination Induces Durable Immune Memory to SARS-CoV-2 with Continued Evolution to Variants of Concern

“…In addition to the production of antibodies, an effective immune response requires the generation of long-lived memory B and T cells. mRNA vaccines induce robust germinal center responses in humans (11), resulting in memory B cells that are specific for both the full-length SARS-CoV-2 Spike protein and the Spike receptor binding domain (RBD) (12)(13)(14). mRNA vaccination has also been shown to generate Spike-specific memory CD4+ and CD8+ T cell responses (15)(16)(17)(18).…”

Vaccination of COVID‐19 convalescent plasma donors increases binding and neutralizing antibodies against SARS‐CoV‐2 variants

“…These data confirm that while natural infections induce nAb and provide a basic level of protection, one or two doses of vaccine are highly efficacious at boosting binding antibody reactivity and nAb titers, which have been demonstrated to increase protection against reinfection and vaccine breakthrough infections, especially from new variants 18,25 . It appears that vaccination following prior infection elicits higher levels of circulating neutralizing Ab, while natural infection stimulates more robust and durable B cell maturation that eventually responds with more potent and broader nAb following a subsequent infection or vaccination 26 . Our findings support the need for future controlled studies using vaccine boosted CCP, particularly in immunosuppressed patients.…”