The emergence of the highly-transmissible novel coronavirus SARS-CoV2 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. Our work will provide preclinical safety, immunogenicity, and efficacy data on leading SARS-CoV2 vaccine platforms that can de-risk human trials in pediatric populations and justify bypassing time consuming and expensive age de-escalation studies.

During the last three decades, three pathogenic zoonotic diseases (SARS, MERS and the recent COVID-19) by novel CoVs have emerged to cause severe respiratory syndromes and varying degrees of mortality in humans. Yet, SARS-CoV-2 has demonstrated high rates of human-to-human transmission that has led to a pandemic of historic proportions. Studying the immunogenicity and efficacy of vaccine-elicited immunity to SARS-CoV-2 in the infant immune system of a highly-relevant animal model will reveal key information on whether infants can mount robust functional anti-CoV responses to leading vaccine candidates, and on whether the SARS-CoV2 vaccine can be incorporated within the pediatric schedule where lifelong immunity and high coverage can be achieved.

Uncovering the immune responses that prevent SARS-CoV-2 replication and disease in pediatric populations is key to identify the appropriate age group for vaccines. We are working on:

1. Development of an infant non-human primate (NHP) model of respiratory infection with a pandemic coronavirus. SARS-CoV replicates in the lungs of primate species and replicates aspects of the human disease, including lung pathology. This first infant model of SARS-CoV-2 infection will reveal important information on viral kinetics, disease course, and impact of vaccine-elicited immunity.

2. Assessment of vaccine-elicited immune responses to SARS-CoV-2 infection in infant rhesus macaques. We will perform a comprehensive analysis of vaccine-elicited adaptive systemic and mucosal immune responses to SARS-CoV2 Spike protein vaccines, and relate these immune responses to rate of infection and lung disease, induction of the associated cytokine storm, as well as duration of viral shedding.

3. Application of SARS-CoV2 systems biology elicited by SARS-CoV-2 vaccination of infants. We have optimized assays for limited pediatric samples sizes and will apply a suite of serological assays, Nanostring technology, and single-cell Proteogenomics to assess vaccine immunogenicity and efficacy.