Immunogenicity and Efficacy of SARS-CoV-2 stabilized prefusion Spike protein vaccines in infant rhesus macaques

ABSTRACTThe emergence of the highly-transmissible novel coronavirus SARS-CoV2 has led to a global pandemic ofsevere 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, itwill be important to develop a vaccine that can be administered in early life and generate long term immunity toend 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 highrates of pediatric vaccine coverage and potential for lifelong immunity. In fact, infants can respond remarkablywell to protein antigens, including the hepatitis B and candidate HIV envelope vaccines, and there is evidencethat HIV-infected infants are better equipped to generate HIV-neutralizing antibodies. Moreover, our previouswork in human and rhesus monkeys has established that infants are able to generate HIV Env vaccineresponses of comparable or higher magnitude to that of adults that persist for months and are able to beboosted. 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 nonhumanprimate model and determine their efficacy against HIV acquisition in adolescence. As related complementarystudies, we propose to assess the immunogenicity and efficacy of candidate SARS-CoV2 spike (S) protein andmRNA vaccine candidates in infant rhesus monkeys. We hypothesize that infants can mount effective andpersistent systemic and mucosal antibody responses to SARS-CoV-2 vaccination that will protectagainst virus challenge. This work will provide preclinical safety, immunogenicity, and efficacy data onleading SARS-CoV2 vaccine platforms that can de-risk human trials in pediatric populations and justifybypassing time consuming and expensive age de-escalation studies. The end of the SARS-CoV2 pandemicwill 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.