Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection

TLDR

The COVID‑19 pandemic remains difficult to control more than a year after its start, as emerging variants are more transmissible and resistant to antibodies despite available vaccines. Broad neutralizing responses arise from ongoing somatic mutation, clonal turnover of memory B cells, and selective retention and expansion of broad, potent antibody clones that are resistant to RBD mutations, especially after vaccination. In unvaccinated convalescents, RBD reactivity, neutralization, and memory B cells remain stable from 6 to 12 months, while vaccination boosts all humoral components and elicits neutralization of variants comparable to or exceeding that of vaccine‑naïve individuals, indicating durable and protective immunity.

Abstract

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 antibodies 1,2 . 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 vaccines 3,4 . 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 individuals 2,5–8 . 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 concern 4,9 . 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.