Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs

Emerging SARS-CoV-2 variants raise concerns on protective immunity. Here the authors show that convalescent sera from people infected with Alpha, Beta, Gamma or Delta show a significant drop of Omicron-BA.1 neutralization and that vaccine-breakthrough infections with Omicron-BA.1 or Delta result in robust neutralization for both Delta and Omicron-BA.1. Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.

Automated summary

Emerging SARS-CoV-2 variants pose concerns about protective immunity, as convalescent sera from individuals infected with different variants show reduced neutralization against Omicron-BA.1. However, vaccine-breakthrough infections with Omicron-BA.1 or Delta lead to robust neutralization against both variants. Understanding the antigenic relationship between variants is crucial due to the complexity of population immunity resulting from prior infections and vaccinations.