Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost

作者：Bo Zhang, Youyi Fong, Lauren Dang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine Rouphael, Angela R Branche, David Diemert, Ann R. Falsey, Daniel S. Graciaa, Lindsey R. Baden, Sharon E. Frey, Jennifer A. Whitaker, Susan J. Little, Satoshi Kamidani, Emmanuel B. Walter, Richard Novák, Richard Rupp, Lisa A. Jackson, Chenchen Yu, Craig A. Magaret, Cindy Molitor, Bhavesh Borate, Sydney Busch, David Benkeser, Antonia Netzl, Derek J. Smith, Tara M Babu, Angelica C Kottkamp, Anne F. Luetkemeyer, Lilly Cheng Immergluck, Rachel M. Presti, Martín Bäcker, Patricia Winokur, Siham Mahgoub, Paul Goepfert, Dahlene N. Fusco, Robert L. Atmar, Christine M. Posavad, Jinjian Mu, Mat Makowski, Mamodikoe Makhene, Seema Nayak, Paul C. Roberts, Peter B. Gilbert, Dean Follmann, Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-55931-w · 被引用次数：10 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、Long-Term Effects of COVID-19

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.