Journal Article

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

Posavad, Christine M., Novak, Richard M., Winokur, Patricia L., Follmann, Dean, Mahgoub, Siham M., Atmar, Robert L., Bäcker, Martín, Fusco, Dahlene N., Dang, Lauren, Baden, Lindsey R., Fong, Youyi, Jackson, Lisa A., Immergluck, Lilly C., Falsey, Ann R., Nayak, Seema U., Frey, Sharon E., Zhang, Bo, Kamidani, Satoshi, Borate, Bhavesh, Fintzi, Jonathan, Molitor, Cindy, Netzl, Antonia, Babu, Tara M., Busch, Sydney, Makhene, Mamodikoe K., Mu, Jinjian, Roberts, Paul C., Wang, Jing, Yu, Chenchen, Gilbert, Peter B., Chen, Shiyu, Rupp, Richard, Diemert, David J., Graciaa, Daniel S., Benkeser, David, Rouphael, Nadine G., Little, Susan J., Smith, Derek J., Whitaker, Jennifer A., Magaret, Craig A., Presti, Rachel M., Luetkemeyer, Anne F., Makowski, Mat, Walter, Emmanuel B., Branche, Angela R., Kottkamp, Angelica C., Goepfert, Paul A.

2025

Overview

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. Here the authors analyze data from COVAIL trial participants receiving an mRNA second COVID-19 vaccine boost and show that, while neutralizing antibody titer is correlated with Omicron COVID-19 risk, the correlation is weak in naïve individuals compared to previously infected ones. _

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 631/250/2152/2153/1291 / 631/250/590/2293 / 639/705/531 / 692/308 / 692/699/255 / 82/1 / Adult / Antibodies / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / Antibodies, Viral - blood / Antibodies, Viral - immunology / Correlation / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 - virology / COVID-19 vaccines / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - immunology / Exposure / Female / Humanities and Social Sciences / Humans / Immunization, Secondary - methods / Inserts / Male / Middle Aged / mRNA / mRNA Vaccines / multidisciplinary / Neutralization / Neutralizing / Pandemics / Prototypes / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - immunology / Vaccines / Vaccines, Synthetic - immunology / Viral diseases