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 SARS-CoV-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.
【초록키워드】 COVID-19, SARS-CoV-2, IgG, ACE2, Vaccine, immune response, immunogenicity, Immunity, S protein, antibody, SARS-COV-2 infection, pediatric, TLR7, memory B cells, Transmission, SARS-CoV-2 vaccines, SARS-CoV-2 vaccine, Lipid nanoparticles, Infant, adverse effects, Protein, Infants, Adults, T cell, Health, RBD, mRNA, immune responses, Impact, S-2P, immune function, group, SARS-CoV-2 infections, T cell response, memory B cell, IFN-γ, binding, TNF-α, Lipid nanoparticle, cellular response, rhesus macaque, Cellular responses, IL-17, proof of concept, squalene, two groups, neutralizing antibody titers, domain, TLR7/8, immunogenic, proof, severe complications, novel vaccines, prefusion, blocking activity, transmission of SARS-CoV-2, Moderna mRNA-1273 vaccine, Inclusion, mitigate, Prevent, limit, decrease, immunized, peaking, S1 and S2, eight, magnitude, elicited, purified, severe complication, intramuscularly, the SARS-CoV-2, 【제목키워드】 immune response, SARS-CoV-2 vaccine, rhesus macaque, elicit,