Abstract
More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals2,5–8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.
Highlights
Antibody reactivity in plasma to the receptor binding domain (RBD) and nucleoprotein (N) were measured by enzyme-linked immunosorbent assay (ELISA)[3]
Convalescent participants who had not been vaccinated maintained most of their anti-RBD IgM (103%), IgG (82%) and IgA (72%) titres between 6 and 12 months after infection (Fig. 1a, Extended Data Fig. 2a–k)
Neutralizing activity was directly correlated with IgG anti-RBD (Extended Data Fig. 2p) but not with anti-N titres (Extended Data Fig. 2q, r)
Summary
During immune responses, activated B cells interact with cognate T cells and begin dividing before selection into the plasma cell, memory or germinal centre B cell compartments, partly on the basis of their affinity for antigen[17,27,28,29,30,31]. Consistent with the longevity of bone marrow plasma cells, infection with SARS-CoV-2 leads to persistent anti-RBD antibodies in serum, and corresponding neutralizing responses. SARS-CoV-2 infection produces a memory compartment that continues to evolve more than 12 months after infection with accumulation of somatic mutations, emergence of new clones and increasing affinity, all of which are consistent with long-term persistence of germinal centres. The notable evolution of neutralizing breadth after infection with SARS-CoV-2 and the robust enhancement of serologic responses and B cell memory achieved with mRNA vaccination suggests that convalescent individuals who are vaccinated should enjoy high levels of protection against emerging variants without a need to modify existing vaccines. R. et al Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Stamatatos, L. et al mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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