Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial

Youyi Fong; Yunda Huang; David Benkeser; Lindsay N Carpp; Germán Áñez; Wayne Woo; Alice McGarry; Lisa M Dunkle; Iksung Cho; Christopher R Houchens; Karen Martins; Lakshmi Jayashankar; Flora Castellino; Christos J Petropoulos; Andrew Leith; Deanne Haugaard; Bill Webb; Yiwen Lu; Chenchen Yu; Bhavesh Borate; Lars W P van der Laan; Nima S Hejazi; April K Randhawa; Michele P Andrasik; James G Kublin; Julia Hutter; Maryam Keshtkar-Jahromi; Tatiana H Beresnev; Lawrence Corey; Kathleen M Neuzil; Dean Follmann; Julie A Ake; Cynthia L Gay; Karen L Kotloff; Richard A Koup; Ruben O Donis; Peter B Gilbert; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/2019nCoV-301 Principal Investigators and Study Team; United States Government (USG)/CoVPN Biostatistics Team

doi:10.1038/s41467-022-35768-3

Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial

Nat Commun. 2023 Jan 19;14(1):331. doi: 10.1038/s41467-022-35768-3.

Authors

Youyi Fong^{1

2}, Yunda Huang^{1

3}, David Benkeser⁴, Lindsay N Carpp¹, Germán Áñez⁵, Wayne Woo⁵, Alice McGarry⁵, Lisa M Dunkle⁵, Iksung Cho⁵, Christopher R Houchens⁶, Karen Martins⁶, Lakshmi Jayashankar⁶, Flora Castellino⁶, Christos J Petropoulos⁷, Andrew Leith⁸, Deanne Haugaard⁸, Bill Webb⁸, Yiwen Lu¹, Chenchen Yu¹, Bhavesh Borate¹, Lars W P van der Laan^{1

9}, Nima S Hejazi^{1

10}, April K Randhawa¹, Michele P Andrasik¹, James G Kublin¹, Julia Hutter¹¹, Maryam Keshtkar-Jahromi¹¹, Tatiana H Beresnev¹¹, Lawrence Corey^{1

12}, Kathleen M Neuzil¹³, Dean Follmann¹⁴, Julie A Ake¹⁵, Cynthia L Gay¹⁶, Karen L Kotloff¹³, Richard A Koup^#¹⁷, Ruben O Donis^#⁶, Peter B Gilbert^#^{18

19

20}; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/2019nCoV-301 Principal Investigators and Study Team; United States Government (USG)/CoVPN Biostatistics Team

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
² Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Department of Global Health, University of Washington, Seattle, WA, 98195, USA.
⁴ Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
⁵ Novavax, Inc., Gaithersburg, MD, USA.
⁶ Biomedical Advanced Research and Development Authority, Washington, DC, USA.
⁷ LabCorp-Monogram Biosciences, South San Francisco, CA, USA.
⁸ Nexelis, Seattle, WA, USA.
⁹ Department of Statistics, University of Washington, Seattle, WA, USA.
¹⁰ Department of Biostatistics, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
¹¹ Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, USA.
¹² Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹³ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁴ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹⁶ University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹⁷ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁸ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. pgilbert@fredhutch.org.
¹⁹ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. pgilbert@fredhutch.org.
²⁰ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA. pgilbert@fredhutch.org.

^# Contributed equally.

Abstract

In the PREVENT-19 phase 3 trial of the NVX-CoV2373 vaccine (NCT04611802), anti-spike binding IgG concentration (spike IgG), anti-RBD binding IgG concentration (RBD IgG), and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks post-dose two are assessed as correlates of risk and as correlates of protection against COVID-19. Analyses are conducted in the U.S. cohort of baseline SARS-CoV-2 negative per-protocol participants using a case-cohort design that measures the markers from all 12 vaccine recipient breakthrough COVID-19 cases starting 7 days post antibody measurement and from 639 vaccine recipient non-cases. All markers are inversely associated with COVID-19 risk and directly associated with vaccine efficacy. In vaccine recipients with nAb ID50 titers of 50, 100, and 7230 international units (IU50)/ml, vaccine efficacy estimates are 75.7% (49.8%, 93.2%), 81.7% (66.3%, 93.2%), and 96.8% (88.3%, 99.3%). The results support potential cross-vaccine platform applications of these markers for guiding decisions about vaccine approval and use.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19* / prevention & control
Clinical Trials, Phase III as Topic
Humans
Immunoglobulin G
SARS-CoV-2
Vaccine Efficacy

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G

Abstract

Publication types

MeSH terms

Substances

Grants and funding