ABSTRACT The emergence of the highly-transmissible novel coronavirus SARS-CoV-2 has led to a global pandemic of severe respiratory disease. While elderly individuals and adults with co-morbidities are high risk populations, coronavirus disease (COVID-19) can occur in individuals across all age groups, including infants. Therefore, it will be important to develop a vaccine that can be administered in early life and generate long term immunity to end the COVID19 pandemic. While initial safety testing of vaccine candidates will occur in adult populations, there are many potential advantages of targeting the vaccine to the pediatric vaccine schedule including high rates of pediatric vaccine coverage and potential for lifelong immunity. In fact, infants can respond remarkably well to protein antigens, including the hepatitis B and candidate HIV envelope vaccines, and there is evidence that HIV-infected infants are better equipped to generate HIV-neutralizing antibodies. Moreover, our previous work in human and rhesus monkeys has established that infants are able to generate HIV Env vaccine responses of comparable or higher magnitude to that of adults that persist for months and are able to be boosted. The parent grant P01 AI117915-06 “Early Life Vaccination to Prevent HIV Acquisition in Adolescence” aims to assess candidate HIV envelope mRNA and SOSIP trimer vaccines in infant rhesus monkey nonhuman primate model and determine their efficacy against HIV acquisition in adolescence. As related complementary studies, we propose to assess the immunogenicity and efficacy of candidate SARS-CoV-2 spike (S) protein and mRNA vaccine candidates in infant rhesus monkeys. We hypothesize that infants can mount effective and persistent systemic and mucosal antibody responses to SARS-CoV-2 vaccination that will protect against virus challenge. This work will provide preclinical safety, immunogenicity, and efficacy data on leading SARS-CoV-2 vaccine platforms that can de-risk human trials in pediatric populations and justify bypassing time consuming and expensive age de-escalation studies. The end of the SARS-CoV-2 pandemic will require high global coverage with a vaccine that prevents viral spread and generates long lasting immunity, which may best be achieved with a pediatric targeted vaccine.

PUBLIC HEALTH NARRATIVE The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease (COVID-19) of 2019-2020 has led to pandemic of unprecedented scale that requires immediate action for countermeasures. A vaccine is considered the best option to contain the virus and to prevent further outbreaks. This work will provide preclinical data on leading SARS-CoV-2 vaccines platforms that can de-risk human trials in pediatric populations. The end of the SARS-CoV-2 pandemic will require high global coverage with a vaccine that prevents viral spread and generates long lasting immunity, which may best be achieved with a pediatric targeted vaccine.