Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost
Abstract
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.
Article Details
Authors (47)
Bo Zhang
Youyi Fong
Lauren Dang
Jonathan Fintzi
Shiyu Chen
Jing Wang
Hunan Cancer Hospital Changsha China
Nadine G. Rouphael
Angela R. Branche
David J. 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 M. Novak
Division of Infectious Diseases, University of Illinois Health Sciences, Chicago
Richard Rupp
Lisa A. Jackson
Kaiser Permanente Washington Health Research Institute, Seattle
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
Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco
Lilly C. Immergluck
Rachel M. Presti
Martín Bäcker
Patricia L. Winokur
Siham M. Mahgoub
Paul A. Goepfert
Department of Medicine, University of Alabama at Birmingham
Dahlene N. Fusco
Robert L. Atmar
Department of Molecular Virology and Microbiology, Baylor College of Medicine
Christine M. Posavad
Jinjian Mu
Mat Makowski
Mamodikoe K. Makhene
Seema U. Nayak
Paul C. Roberts
Peter B. Gilbert
Dean Follmann