Language

English

Publication Date

1-17-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-55931-w

PMID

39824819

PMCID

PMC11748719

PubMedCentral® Posted Date

1-17-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.

Keywords

Humans, Antibodies, Neutralizing, COVID-19, COVID-19 Vaccines, SARS-CoV-2, Antibodies, Viral, Female, Male, Immunization, Secondary, Middle Aged, Adult, Spike Glycoprotein, Coronavirus, mRNA Vaccines, Vaccines, Synthetic, RNA vaccines, Statistics, Medical research, Infectious diseases, Antibodies

Published Open-Access

yes

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