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Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial

Authors :
Ying Huang
Nima S. Hejazi
Bryan Blette
Lindsay N. Carpp
David Benkeser
David C. Montefiori
Adrian B. McDermott
Youyi Fong
Holly E. Janes
Weiping Deng
Honghong Zhou
Christopher R. Houchens
Karen Martins
Lakshmi Jayashankar
Britta Flach
Bob C. Lin
Sarah O’Connell
Charlene McDanal
Amanda Eaton
Marcella Sarzotti-Kelsoe
Yiwen Lu
Chenchen Yu
Avi Kenny
Marco Carone
Chuong Huynh
Jacqueline Miller
Hana M. El Sahly
Lindsey R. Baden
Lisa A. Jackson
Thomas B. Campbell
Jesse Clark
Michele P. Andrasik
James G. Kublin
Lawrence Corey
Kathleen M. Neuzil
Rolando Pajon
Dean Follmann
Ruben O. Donis
Richard A. Koup
Peter B. Gilbert
on behalf of the Immune Assays
Moderna, Inc.
Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE)
United States Government (USG)/CoVPN Biostatistics Teams
Source :
Viruses, Vol 15, Iss 10, p 2029 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs.

Details

Language :
English
ISSN :
19994915
Volume :
15
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.86848c63770d47f1b9459f59b793650a
Document Type :
article
Full Text :
https://doi.org/10.3390/v15102029