Analysis of Antibody Markers as Immune Correlates of Risk of Severe COVID-19 in the PREVENT-19 Efficacy Trial of the NVX-CoV2373 Recombinant Protein Vaccine

作者：Youyi Fong, Yunda Huang, Ying Huang, Wayne Woo, Alice McGarry, Germán Áñez, Lisa M. Dunkle, Iksung Cho, Christopher R. Houchens, Karen Martins, Lakshmi Jayashankar, Flora Castellino, Christos J. Petropoulos, Andrew Leith, Deanne Haugaard, William A. Webb, Yiwen Lu, Chenchen Yu, Lindsay N. Carpp, April K. Randhawa, Michele P. Andrasik, James G. Kublin, Julia Hütter, Maryam Keshtkar‐Jahromi, Tatiana Beresnev, Carina A. Rodriguez, Milagritos D. Tapia, Christine B. Turley, Carmen Zorrilla, Stuart H. Cohen, Susan E Kline, Elizabeth Barranco, Lawrence Corey, Kathleen M. Neuzil, Dean Follmann, Julie A. Ake, Cynthia L. Gay, Karen L. Kotloff, Thomas Jones, Richard A. Koup, Rubén O. Donis, Peter B. Gilbert · 发表于：Clinical Infectious Diseases · 年份：2025 · DOI：10.1093/cid/ciaf558 · 被引用次数：1 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、vaccines and immunoinformatics approaches

BACKGROUND: We previously showed that ancestral-specific anti-Spike binding IgG concentration and 50% inhibitory dilution neutralizing antibody titer (nAb-ID50) measured at 2 weeks postdose 2 (∼peak) were inverse correlates of risk (CoRs) of COVID-19 over 2 months post ∼peak in the PREVENT-19 trial of the NVX-CoV2373 vaccine; there were not sufficient data to assess CoRs of severe COVID-19. METHODS: Here, we assessed, in the same vaccinated cohort, Delta- and ancestral-specific Spike IgG and nAb-ID50 at ∼peak and over time as CoRs of severe COVID-19 and of Delta COVID-19 over 3.5-10 months post ∼peak (287 breakthrough Delta cases, including 8 severe; 446 noncases). RESULTS: Peak antibody levels were much higher for noncases versus severe cases (all inferred Delta), with nAb-ID50 Delta geometric mean 209.5 arbitrary units (AU)/mL (95% CI: 176.1, 249.1) versus 9.6 AU/mL (95% CI: 2.4, 38.6), respectively. Frequency of detectable nAb-ID50 titer was 98.3% (97.2, 99.0) for noncases versus 62.5% (22.3, 93.9) for severe cases. All markers were inverse CoRs of severe COVID-19, with a ∼peak hazard ratio (HR) of 0.13 (95% CI: .03, .57) per 10-fold nAb-ID50 Delta increase. Severe COVID-19 risk through 305 days postday 35 was 0.0338 (0.0043, 0.206) at the nAb-ID50 Delta 2.5th percentile (8.4 AU/mL), and 0.002 (0.0000, 0.0108) and 0.0002 (0.0000, 0.0035) at the 50th and 95th percentiles (210, 2522 AU/mL). CONCLUSIONS: Postvaccination NVX-CoV2373 antibody levels are stronger predictors of s...