Correlates of immunity in SARS-CoV-2 post-vaccine infections in the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) Study

Abstract

Abstract Background: We sought to determine pre-infection correlates of immunity against SARS-CoV-2 post-vaccine infections. Methods: Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of WT SARS-CoV-2 Spike (S)-specific IgG and IgA antibodies using a microsphere-based multiplex immunoassay. Serum samples were also assessed for neutralization activity against D614G, Delta (617.2), and Omicron BA.1 and BA.1.1 variants using a lentiviral pseudovirus neutralization assay. After the fall visit, participants reported all positive PCR and/or antigen tests for SARS-CoV-2. Duration, severity, and type of symptoms, as well as risk exposures and adherence to precautionary measures, were assessed by questionnaires during the spring 2022 visit. Results: Thirty-two participants (18.2%) had infections between December 7, 2021 and April 1, 2022. Pre-infection anti-S IgG antibody levels and neutralizing titers against BA.1 and BA.1.1 were higher in individuals that did not develop infection (p values 0.0098, 0.0313, and 0.021, respectively). No individuals with an anti-S level greater than 15,000 binding antibody units (BAU/ml) developed a post-vaccine infection. Conclusion: High serum anti-S IgG antibody levels, high neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against post-vaccine infections during the initial Omicron wave. BAU levels greater than 15,000 in the fall of 2021 were associated with complete protection during the initial Omicron wave. This work was supported in whole, or in part, with federal funds from the Defense Health Program (HU00012020067, HU00012020094) and the Immunization Healthcare Branch (HU00012120104) of the Defense Health Agency, United States Department of Defense, and the National Institute of Allergy and Infectious Disease (HU00011920111), under Inter-Agency Agreement Y1-AI-5072.