Title

Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later

Authors

Emma C. Milligan, UNC School of Medicine
Katherine Olstad, California National Primate Research Center
Caitlin A. Williams, Weill Cornell Medicine
Michael Mallory, The University of North Carolina at Chapel Hill
Patricio Cano, The University of North Carolina at Chapel Hill
Kaitlyn A. Cross, The University of North Carolina at Chapel Hill
Jennifer E. Munt, The University of North Carolina at Chapel Hill
Carolina Garrido, University of California, Davis
Lisa Lindesmith, The University of North Carolina at Chapel Hill
Jennifer Watanabe, California National Primate Research Center
Jodie L. Usachenko, California National Primate Research Center
Lincoln Hopkins, California National Primate Research Center
Ramya Immareddy, California National Primate Research Center
Yashavanth Shaan Lakshmanappa, University of California, Davis
Sonny R. Elizaldi, University of California, Davis
Jamin W. Roh, University of California, Davis
Rebecca L. Sammak, California National Primate Research Center
Rachel E. Pollard, School of Veterinary Medicine
Jo Ann L. Yee, California National Primate Research Center
Savannah Herbek, Weill Cornell Medicine
Trevor Scobey, The University of North Carolina at Chapel Hill
Dieter Miehlke, Duke University School of Medicine
Genevieve Fouda, Duke University School of Medicine
Guido Ferrari, Duke University School of Medicine
Hongmei Gao, Duke University School of Medicine
Xiaoying Shen, Duke University School of Medicine
Pamela A. Kozlowski, LSU Health Sciences Center - New OrleansFollow
David Montefiori, Duke University School of Medicine

Document Type

Article

Publication Date

12-1-2022

Publication Title

Science Translational Medicine

Abstract

The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.

First Page

eadd6383

PubMed ID

36454813

Volume

15

Issue

685

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