Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод в очереди
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Milligan Emma C, Olstad Katherine, Williams Caitlin A, Mallory Michael, Cano Patricio, Cross Kaitlyn A, Munt Jennifer E, Garrido Carolina, Lindesmith Lisa, Watanabe Jennifer, Usachenko Jodie L, Hopkins Lincoln, Immareddy Ramya, Shaan Lakshmanappa Yashavanth, Elizaldi Sonny R, Roh Jamin W, Sammak Rebecca L, Pollard Rachel E, Yee JoAnn L, Herbek Savannah, Scobey Trevor, Miehlke Dieter, Fouda Genevieve, Ferrari Guido, Gao Hongmei, Shen Xiaoying, Kozlowski Pamela A, Montefiori David, Hudgens Michael G, Edwards Darin K, Carfi Andrea, Corbett Kizzmekia S, Graham Barney S, Fox Christopher B, Tomai Mark, Iyer Smita S, Baric Ralph, Reader Rachel, Dittmer Dirk P, Van Rompay Koen K A, Permar Sallie R, De Paris Kristina
Аннотация
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.