Towards a population-based threshold of protection for COVID-19 vaccines
David Goldblatt, Andrew Fioré-Gartland, Marina Johnson, Adam Hunt, Christopher Bengt, Dace Zavadska, Hilda Darta Snipe, Jeremy Brown, Lesley Workman, Heather J. Zar, David C. Montefiori, Xiaoying Shen, Peter Dull, Stanley A. Plotkin, George R. Siber, Donna M. Ambrosino
Abstract
Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42-559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35-102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.