The inclusion of infants in the SARS-CoV-2 vaccine rollout 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 SARSCoV- 2 vaccines. Two groups of eight 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, amino-terminal 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.
American Association for the Advancement of Science [Society Publisher]
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Garrido, Carolina; Curtis, Alan D.; Dennis, Maria; Pathak, Sachi H.; Gao, Hongmei; Montefiori, David; Tomai, Mark; Fox, Christopher B.; Kozlowski, Pamela A.; Scobey, Trevor; Munt, Jennifer E.; Mallory, Michael L.; Saha, Pooja T.; Hudgens, Michael G.; Lindesmith, Lisa C.; Baric, Ralph S.; Abiona, Olubukola M.; Graham, Barney S.; Corbett, Kizzmekia S.; and Edwards, Darin, "SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques" (2021). School of Graduate Studies Faculty Publications. 31.