Naturally enhanced neutralizing breadth to SARS-CoV-2 after one year

Abstract

Over 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 excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies. Here we report on a cohort of 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 and 12 months after infection, 41% of whom also received mRNA vaccines. 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 from 6 to 12 months. Vaccination increases all components of the humoral response, and as expected, results in serum neutralizing activities against variants of concern that are comparable to or greater than neutralizing activity against the original Wuhan Hu-1 achieved by vaccination of naive individuals. 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 variants of concern. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand dramatically 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. Should memory responses evolve in a similar manner in vaccinated individuals, additional appropriately timed boosting with available vaccines could cover most circulating variants of concern.

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

“…3b). Therefore, our results extend previous results obtained with other variants, showing that a single dose of vaccine boosts crossneutralizing antibody responses 17,[42][43][44][45] .…”

Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection

“… 10 This remains to be validated in future studies. Interestingly, the breadth of cross-neutralization appears to increase over time following natural infections 32 but whether then same will occur after vaccination remains to be understood.…”

Long-Lasting Immunity Against SARS-CoV-2: Dream or Reality?

“…Our results reveal that in most cases, SARS-CoV-2 S-specific IgG levels remained stable over time and SARS-CoV-2 NCP-specific IgG levels decreased to a stable level within 6–12 months after symptom onset, while their range continuously diminished. Recent studies show that SARS-CoV-2-specific antibody levels after an infection were detectable in the majority of donors over a period of up to 1 year, even though the rate of recession varied ( 9 , 11 , 12 , 26 , 27 ). This supports our findings from the long-term analysis.…”