Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Kizzmekia S Corbett; Martha C Nason; Britta Flach; Matthew Gagne; Sarah O'Connell; Timothy S Johnston; Shruti N Shah; Venkata Viswanadh Edara; Katharine Floyd; Lilin Lai; Charlene McDanal; Joseph R Francica; Barbara Flynn; Kai Wu; Angela Choi; Matthew Koch; Olubukola M Abiona; Anne P Werner; Juan I Moliva; Shayne F Andrew; Mitzi M Donaldson; Jonathan Fintzi; Dillon R Flebbe; Evan Lamb; Amy T Noe; Saule T Nurmukhambetova; Samantha J Provost; Anthony Cook; Alan Dodson; Andrew Faudree; Jack Greenhouse; Swagata Kar; Laurent Pessaint; Maciel Porto; Katelyn Steingrebe; Daniel Valentin; Serge Zouantcha; Kevin W Bock; Mahnaz Minai; Bianca M Nagata; Renee van de Wetering; Seyhan Boyoglu-Barnum; Kwanyee Leung; Wei Shi; Eun Sung Yang; Yi Zhang; John-Paul M Todd; Lingshu Wang; Gabriela S Alvarado; Hanne Andersen; Kathryn E Foulds; Darin K Edwards; John R Mascola; Ian N Moore; Mark G Lewis; Andrea Carfi; David Montefiori; Mehul S Suthar; Adrian McDermott; Mario Roederer; Nancy J Sullivan; Daniel C Douek; Barney S Graham; Robert A Seder

doi:10.1126/science.abj0299

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Science. 2021 Sep 17;373(6561):eabj0299. doi: 10.1126/science.abj0299. Epub 2021 Sep 17.

Authors

Kizzmekia S Corbett^#¹, Martha C Nason^#², Britta Flach¹, Matthew Gagne¹, Sarah O'Connell¹, Timothy S Johnston¹, Shruti N Shah¹, Venkata Viswanadh Edara³, Katharine Floyd³, Lilin Lai³, Charlene McDanal⁴, Joseph R Francica¹, Barbara Flynn¹, Kai Wu⁵, Angela Choi⁵, Matthew Koch⁵, Olubukola M Abiona¹, Anne P Werner¹, Juan I Moliva¹, Shayne F Andrew¹, Mitzi M Donaldson¹, Jonathan Fintzi¹, Dillon R Flebbe¹, Evan Lamb¹, Amy T Noe¹, Saule T Nurmukhambetova¹, Samantha J Provost¹, Anthony Cook⁶, Alan Dodson⁶, Andrew Faudree⁶, Jack Greenhouse⁶, Swagata Kar⁶, Laurent Pessaint⁶, Maciel Porto⁶, Katelyn Steingrebe⁶, Daniel Valentin⁶, Serge Zouantcha⁶, Kevin W Bock⁷, Mahnaz Minai⁷, Bianca M Nagata⁷, Renee van de Wetering¹, Seyhan Boyoglu-Barnum¹, Kwanyee Leung¹, Wei Shi¹, Eun Sung Yang¹, Yi Zhang¹, John-Paul M Todd¹, Lingshu Wang¹, Gabriela S Alvarado¹, Hanne Andersen⁶, Kathryn E Foulds¹, Darin K Edwards⁵, John R Mascola¹, Ian N Moore⁷, Mark G Lewis⁶, Andrea Carfi⁵, David Montefiori⁴, Mehul S Suthar^{3

8}, Adrian McDermott¹, Mario Roederer¹, Nancy J Sullivan¹, Daniel C Douek¹, Barney S Graham¹, Robert A Seder¹

Affiliations

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
² Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³ Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Department of Pediatrics, Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA.
⁴ Department of Surgery, Duke University Medical Center, Durham, NC 27708, USA.
⁵ Moderna Inc., Cambridge, MA 02139, USA.
⁶ Bioqual Inc., Rockville, MD 20850, USA.
⁷ Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Department of Microbiology and Immunology, Atlanta, GA 30329, USA.

^# Contributed equally.

Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti–S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273–induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine–induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

Publication types

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

MeSH terms

2019-nCoV Vaccine mRNA-1273
Animals
Antibodies, Neutralizing / blood*
Antibodies, Neutralizing / immunology
Antibodies, Viral / blood*
Antibodies, Viral / immunology
Antibody Affinity
Bronchoalveolar Lavage Fluid / immunology
Bronchoalveolar Lavage Fluid / virology
CD4-Positive T-Lymphocytes / immunology
COVID-19 / immunology
COVID-19 / prevention & control*
COVID-19 / virology
COVID-19 Vaccines / administration & dosage*
COVID-19 Vaccines / immunology*
Female
Immunization Schedule
Immunization, Passive
Immunization, Secondary
Immunogenicity, Vaccine*
Immunoglobulin G / immunology
Immunologic Memory
Lung / immunology
Lung / virology
Macaca mulatta
Male
Mesocricetus
Nasal Mucosa / immunology
Nasal Mucosa / virology
SARS-CoV-2 / immunology*
SARS-CoV-2 / physiology
Spike Glycoprotein, Coronavirus / immunology
Vaccination
Vaccine Potency
Virus Replication

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
2019-nCoV Vaccine mRNA-1273

Grants and funding

ZIA AI005150/ImNIH/Intramural NIH HHS/United States