Variant-specific antibody correlates of protection against SARS-CoV-2 Omicron symptomatic overall infections

Vaccination prior infection elicit neutralizing antibodies targeting SARS-CoV-2, yet the quantitative relationship between serum antibodies infection risk against viral variants remains uncertain, particularly in underrepresented regions.

We investigated the protective correlation of pre-exposure serum neutralizing antibody levels, employing a panel of SARS-CoV-2 pseudoviruses (Omicron BA.1, Omicron BA.2, ancestral D614G), Spike-binding antibody levels, with symptomatic BA.1 or BA.2 SARS-CoV-2 infections overall infection, in 345 household contacts from a SARS-CoV-2 household cohort study.

A four-fold increase in homotypic-neutralizing (e.g., BA.1-neutralizing vs. BA.1 exposure) titers was correlated with protection from symptomatic infections (BA.1 protection: 28% [95%CI 12-42%]; BA.2 protection: 43% [20-62%]), ancestral-neutralizing titers were also correlated with protection from either variant, but only at higher average levels than homotypic. Mediation analyses revealed that homotypic D614G-neutralizing antibodies mediated protection from infection symptomatic infection both from prior infection vaccination.

These findings underscore the importance of monitoring variant-specific antibody responses highlight that antibodies targeting circulating strains may be more predictive of protection from infection. Nevertheless, ancestral-strain-neutralizing antibodies remain relevant as a correlate of protection. Our study emphasizes the need for continued efforts to assess antibody correlates of protection.

We acknowledge funding from the U.S. N.I.H., the Open Philanthropy Project, the Bill Melinda Gates Foundation.