Plasma Neutralization of the SARS-CoV-2 Omicron Variant

Summary: After infection with SARS-CoV-2, antibody levels against the spike protein decrease significantly, but the number of memory B cells remain unchanged, indicating an evolving humoral response at 6.2 months after infection.

Summary: Despite challenges posed by COVID-19 variants, convalescent individuals receiving mRNA vaccines exhibit robust and long-lasting immune responses against circulating SARS-CoV-2 variants, providing hope for effective control of the pandemic.

Summary: The number and variability of neutralizing epitopes targeted by polyclonal antibodies in individuals who have recovered from SARS-CoV-2 or been vaccinated play a crucial role in determining the breadth of neutralization and the genetic barrier to viral escape. Studying HIV-1 pseudotypes and plasma selection experiments, it was found that human polyclonal antibodies target multiple neutralizing epitopes within and outside the receptor-binding domain, and antibody targets coincide with spike sequences enriched for diversity in natural SARS-CoV-2 populations. Combining plasma-selected spike substitutions led to the generation of 'polymutant' spike protein pseudotypes that resist neutralization by polyclonal antibodies to a similar extent as circulating variants of concern. Plasma from individuals who had been infected with SARS-CoV-2 and subsequently received mRNA vaccination was able to neutralize highly resistant SARS-CoV-2 variants, suggesting that optimally elicited polyclonal antibodies can provide protection against future SARS-CoV-2 variations and potential sarbecovirus pandemics.