Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung

• Type of Material: Article
• Authors: Matthew Gagne, National Institute of Allergy and Infectious Diseases; Kizzmekia S Corbett, National Institute of Allergy and Infectious Diseases; Barbara J Flynn, National Institute of Allergy and Infectious Diseases; Kathryn E Foulds, National Institute of Allergy and Infectious Diseases; Danielle A Wagner, National Institute of Allergy and Infectious Diseases; Shayne F Andrew, National Institute of Allergy and Infectious Diseases; John-Paul M Todd, National Institute of Allergy and Infectious Diseases; Christopher C Honeycutt, National Institute of Allergy and Infectious Diseases; Lauren McCormick, National Institute of Allergy and Infectious Diseases; Saule T Nurmukhambetova, National Institute of Allergy and Infectious Diseases; Meredith E Davis-Gardner, Emory University; Laurent Pessaint, BIOQUAL Inc.; Kevin W Bock, National Institute of Allergy and Infectious Diseases; Bianca M Nagata, National Institute of Allergy and Infectious Diseases; Mahnaz Minai, National Institute of Allergy and Infectious Diseases; Anne P Werner, National Institute of Allergy and Infectious Diseases; Juan Moliva, National Institute of Allergy and Infectious Diseases; Courtney Tucker, National Institute of Allergy and Infectious Diseases; Cynthia G Lorang, National Institute of Allergy and Infectious Diseases; Bingchun Zhao, National Institute of Allergy and Infectious Diseases; Elizabeth McCarthy, National Institute of Allergy and Infectious Diseases; Anthony Cook, BIOQUAL Inc.; Alan Dodson, BIOQUAL Inc.; I-Ting Teng, National Institute of Allergy and Infectious Diseases; Prakriti Mudvari, National Institute of Allergy and Infectious Diseases; Jesmine Roberts-Torres, National Institute of Allergy and Infectious Diseases; Farida Laboune, National Institute of Allergy and Infectious Diseases; Lingshu Wang, National Institute of Allergy and Infectious Diseases; Adrienne Goode, BIOQUAL Inc.; Swagata Kar, BIOQUAL Inc.; Seyhan Boyoglu-Barnum, National Institute of Allergy and Infectious Diseases; Eun S Yang, National Institute of Allergy and Infectious Diseases; Wei Shi, National Institute of Allergy and Infectious Diseases; Aurélie Ploquin, National Institute of Allergy and Infectious Diseases; Nicole Doria-Rose, National Institute of Allergy and Infectious Diseases; Andrea Carfi, Moderna Inc; John R Mascola, National Institute of Allergy and Infectious Diseases; Eli A Boritz, National Institute of Allergy and Infectious Diseases; Darin K Edwards, Moderna Inc; Hanne Andersen, BIOQUAL Inc.; Mark G Lewis, BIOQUAL Inc.; Mehul Suthar, Emory University; Barney S Graham, National Institute of Allergy and Infectious Diseases; Mario Roederer, National Institute of Allergy and Infectious Diseases; Ian Moore, Emory University; Martha C Nason, National Institute of Allergy and Infectious Diseases; Nancy J Sullivan, National Institute of Allergy and Infectious Diseases; Daniel C Douek, National Institute of Allergy and Infectious Diseases; Robert A Seder, National Institute of Allergy and Infectious Diseases
• Language: English
• Date: 2022-01-06
• Publisher: CELL PRESS
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Published by Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cell.2021.12.002
• Title of Journal or Parent Work: CELL
• Volume: 185
• Issue: 1
• Start Page: 113
• End Page: +
• Grant/Funding Information: This project has been funded in part by both the Intramural Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services and under HHSN272201400004C (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS) and NIH P51 OD011132 awarded to Emory University. This work was also supported in part by the Emory Executive Vice President for Health Affairs Synergy Fund award, COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, and Woodruff Health Sciences Center 2020 COVID-19 CURE Award.
• Keywords: ADULTS; Life Sciences & Biomedicine; RNA; Cell Biology; BINDING; Biochemistry & Molecular Biology; EXPRESSION; CELLS; NEUTRALIZATION; Science & Technology; INFECTION
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health

Abstract

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID50 at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log10 compared with control animals. In nasal swabs, sgRNA was reduced by 1-log10, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.