Predicting Vaccine Effectiveness for Hospitalization and Symptomatic Disease for Novel SARS-CoV-2 Variants Using Neutralizing Antibody Titers

The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to reduced vaccine effectiveness (VE) and the need for new vaccines or vaccine doses if the extent of immune evasion is severe. Neutralizing antibody titers have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens, and could be used to quickly estimate vaccine effectiveness for new variants. However, no model currently exists to provide precise VE estimates for a new variant against severe disease for SARS-CoV-2 using robust datasets from several populations. We developed predictive models for VE against COVID-19 symptomatic disease and hospitalization across a 54-fold range of mean neutralizing antibody titers. For two mRNA vaccines (mRNA-1273, BNT162b2), models fit without Omicron data predicted that infection with the BA.1 Omicron variant increased the risk of hospitalization 2.8-4.4-fold and increased the risk of symptomatic disease 1.7-4.2-fold compared to the Delta variant. Out-of-sample validation showed that model predictions were accurate; all predictions were within 10% of observed VE estimates and fell within the model prediction intervals. Predictive models using neutralizing antibody titers can provide rapid VE estimates, which can inform vaccine booster timing, vaccine design, and vaccine selection for new virus variants.