SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
Carolina Garrido, Alan D. Curtis, Maria Dennis, Sachi Pathak, Hongmei Gao, David C. Montefiori, Mark A. Tomai, Christopher B. Fox, Pamela A. Kozlowski, Trevor Scobey, Jennifer E. Munt, Michael L. Mallory, Pooja T. Saha, Michael G. Hudgens, Lisa C. Lindesmith, Ralph S. Baric, Olubukola M. Abiona, Barney S. Graham, Kizzmekia S. Corbett, Darin K. Edwards, Andrea Carfı́, Genevieve G. Fouda, Koen K. A. Van Rompay, Kristina De Paris, Sallie R. Permar
Abstract
The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.