Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial
In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.
Authors
- Weiping Deng (ORCID: https://orcid.org/0000-0002-9825-3297)
- Gilbert P.B.
- David C. Benkeser (ORCID: https://orcid.org/0000-0002-1019-8343)
- Thomas Jones (ORCID: https://orcid.org/0000-0002-4097-1886)
- Rose Anne Kenny (ORCID: https://orcid.org/0000-0002-9336-8124)
- Jonathan Fintzi (ORCID: https://orcid.org/0000-0002-6361-702X)
- Frances Priddy (ORCID: https://orcid.org/0000-0002-2533-3982)
- Reena Das (ORCID: https://orcid.org/0000-0002-8938-5423)
- Dean A. Follmann (ORCID: https://orcid.org/0000-0003-4073-0393)
- Donis Ruben O.
- Lawrence Corey (ORCID: https://orcid.org/0000-0002-2179-2436)
- Spyros A. Kalams (ORCID: https://orcid.org/0000-0003-0098-7995)
- Youyi Fong (ORCID: https://orcid.org/0000-0002-4230-6863)
- Lakshmi Jayashankar (ORCID: https://orcid.org/0000-0003-3607-7221)
- Chuong Huynh (ORCID: https://orcid.org/0000-0003-1696-8617)
- Gay C.L.
- B Girard (ORCID: https://orcid.org/0000-0001-8156-6046)
- Bhavesh R. Borate (ORCID: https://orcid.org/0000-0001-8392-7634)
- Marco Carone (ORCID: https://orcid.org/0000-0003-2106-0953)
- Karen J. B. Martins (ORCID: https://orcid.org/0000-0002-3400-7214)
- Kublin J.G.
- Neuzil K.M.
- Isabel Reeder (ORCID: https://orcid.org/0009-0009-0374-6768)
- Hui Chen (ORCID: https://orcid.org/0000-0002-1633-6348)
- Biao Zhang (ORCID: https://orcid.org/0000-0001-8334-5175)
- Yu Chen (ORCID: https://orcid.org/0000-0002-1519-4894)
- Yao Lu (ORCID: https://orcid.org/0000-0003-0887-3183)
- El Sahly H.M.
- Huanyu Zhou (ORCID: https://orcid.org/0000-0003-3303-7312)
- Koup R.A.
- Fichtenbaum C.J
- Andrasik M.P
- Janes H.E
- van der Laan L.W.P
- Carpp L.N
- Chu E
- Baden L.R.
- Houchens C.R
- Xiaolin Wang (ORCID: https://orcid.org/0009-0006-2697-9976)
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- UNC Libraries
- Published
- 2024-10-03
- DOI
- https://doi.org/10.17615/18qe-2h49
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- Biomedical Advanced Research and Development Authority
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases