Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, Beta, Delta, and Omicron variants

Mutations to the spike protein of the Omicron variant of SARS-CoV-2 have evolved to an extent not observed in previous variants of concern (VOCs). This raises concerns regarding its potential for increased antibody evasion, with the subsequent ability to cause infections and disease in people presumed to have adequate immunity.

In this study, the authors quantified neutralizing antibody levels in convalescent and vaccinated sera against ancestral SARS-CoV-2 and VOCs. They demonstrated that sera from convalescent individuals (those who experienced a SARS-CoV-2 infection and were not vaccinated) following ancestral SARS-CoV-2 or Delta infection have low neutralizing activity against Omicron. This is in line with what is now being widely observed: that infection with pre-Omicron variants does not prevent subsequent infection with Omicron. Importantly, in individuals who received two doses of an mRNA vaccine following natural infection, there were high levels of neutralizing antibodies against all VOCs, including Omicron. Three doses of authorized mRNA vaccines induced detectable, but lower levels of neutralizing antibodies against VOCs in long-term care residents, as well. This suggests that, while infection plus vaccination can lead to more diverse immune responses, a similar scenario is also possible via vaccination.

Data from this study, along with other published studies, support the utility of third vaccine doses and will help inform future booster vaccination strategies to tackle the ongoing COVID-19 pandemic.