Anti-SARS-CoV-2 receptor-binding domain
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least a year. Meanwhile, memory B cells are expressing increasingly large and potent antibodies that are resistant to the mutations found in the variants of concern1. Accordingly, vaccination of individuals recovering from coronavirus disease 2019 (COVID-19) with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested1,2.
Here, we examine the evolution of memory B cells five months after vaccination with the mRNA vaccine Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) in a cohort of SARS-CoV-2 naïve individuals. Between priming and boosting, memory B cells produce antibodies that develop increased neutralizing activity, but there is no further increase in potency or extent thereafter. Instead, memory B cells that emerge five months after vaccination of naïve individuals express antibodies similar to those that dominate the initial response.
While individual memory antibodies selected over time by natural infection have greater potency and magnitude than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater after vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies of an equivalent magnitude to those obtained by vaccinating convalescent individuals.
Between January 21 and July 20, 2021, we recruited 32 volunteers with no history of SARS-CoV-2 infection receiving either Moderna (mRNA-1273; n=8) or Pfizer-BioNTech (BNT162b2; n=24) mRNA vaccine for sequential blood donation. Paired samples were obtained at two or three time points. Individuals listed as "prime" were sampled an average of 2.5 weeks after receiving their first dose of vaccine.
Individuals who completed their vaccination regimen were sampled an average of 1.3 months after the booster (median = 35.5 days), which is not statistically different from sampling at 1.3 months in our cohort naturally infected3 (median = 38.5 days, P = 0.21). Individuals sampled at 1.3 months were sampled again approximately 5 months after the second dose of vaccine. The volunteers were aged 23-78 years (median = 34.5 years), 53% were male and 47% were female (for details, see Methods and Supplementary Tables 1 and 2).
Plasma IgM, IgG and IgA responses to the receptor binding domain (RBD) of SARS-CoV-2 were measured by enzyme immunoassay (ELISA)3. As previously reported by others2,4,5,6, there was a significant increase in IgG reactivity to RBD between priming and boosting (P<0.0001) (Fig. 1a). IgM and IgA titers were lower than IgG titers and remained low after the second vaccine dose (Extended Data Fig. 1a,b).
The magnitude of the response was inversely correlated with age after the bonus (r=−0.54, P=0.005), but in this limited sample the age difference was no longer significant at 1.3 or 5 months after the second dose of vaccine (Extended Data Fig. 1c,d). Between 1.3 and 5 months after the booster, the anti-RBD titers of IgG and IgA decreased significantly. IgG titers decreased on average 4.3-fold (range 1.7-10.2-fold) and loss of activity was directly correlated with time after vaccination (P < 0.0001) (Fig. 1a and Extended Data Fig. 1a, be).