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

Matthew Gagne; Kizzmekia S Corbett; Barbara J Flynn; Kathryn E Foulds; Danielle A Wagner; Shayne F Andrew; John-Paul M Todd; Christopher Cole Honeycutt; Lauren McCormick; Saule T Nurmukhambetova; Meredith E Davis-Gardner; Laurent Pessaint; Kevin W Bock; Bianca M Nagata; Mahnaz Minai; Anne P Werner; Juan I Moliva; Courtney Tucker; Cynthia G Lorang; Bingchun Zhao; Elizabeth McCarthy; Anthony Cook; Alan Dodson; I-Ting Teng; Prakriti Mudvari; Jesmine Roberts-Torres; Farida Laboune; Lingshu Wang; Adrienne Goode; Swagata Kar; Seyhan Boyoglu-Barnum; Eun Sung Yang; Wei Shi; Aurélie Ploquin; Nicole Doria-Rose; Andrea Carfi; John R Mascola; Eli A Boritz; Darin K Edwards; Hanne Andersen; Mark G Lewis; Mehul S Suthar; Barney S Graham; Mario Roederer; Ian N Moore; Martha C Nason; Nancy J Sullivan; Daniel C Douek; Robert A Seder

doi:10.1016/j.cell.2021.12.002

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

Cell. 2022 Jan 6;185(1):113-130.e15. doi: 10.1016/j.cell.2021.12.002. Epub 2021 Dec 3.

Authors

Matthew Gagne¹, Kizzmekia S Corbett¹, Barbara J Flynn¹, Kathryn E Foulds¹, Danielle A Wagner¹, Shayne F Andrew¹, John-Paul M Todd¹, Christopher Cole Honeycutt¹, Lauren McCormick¹, Saule T Nurmukhambetova¹, Meredith E Davis-Gardner², Laurent Pessaint³, Kevin W Bock⁴, Bianca M Nagata⁴, Mahnaz Minai⁴, Anne P Werner¹, Juan I Moliva¹, Courtney Tucker¹, Cynthia G Lorang¹, Bingchun Zhao¹, Elizabeth McCarthy¹, Anthony Cook³, Alan Dodson³, I-Ting Teng¹, Prakriti Mudvari¹, Jesmine Roberts-Torres¹, Farida Laboune¹, Lingshu Wang¹, Adrienne Goode³, Swagata Kar³, Seyhan Boyoglu-Barnum¹, Eun Sung Yang¹, Wei Shi¹, Aurélie Ploquin¹, Nicole Doria-Rose¹, Andrea Carfi⁵, John R Mascola¹, Eli A Boritz¹, Darin K Edwards⁵, Hanne Andersen³, Mark G Lewis³, Mehul S Suthar², Barney S Graham¹, Mario Roederer¹, Ian N Moore⁴, Martha C Nason⁶, Nancy J Sullivan¹, Daniel C Douek⁷, Robert A Seder⁸

Affiliations

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
² Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
³ Bioqual, Inc., Rockville, MD 20850, USA.
⁴ Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
⁵ Moderna Inc., Cambridge, MA 02139, USA.
⁶ Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].
⁸ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: [email protected].

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.

Keywords: B cells; COVID-19; Delta; SARS-CoV-2; T cells; anamnestic; antibody; mRNA vaccine; mucosal immunity; nonhuman primates.

Abstract

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