Adaptive Immunity and Persistent SARS-CoV-2 Replication

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Project Summary/Abstract The novel coronavirus SARS-CoV-2 (SARS2) pandemic has so far infected greater than 65 million individuals and resulted in almost 850,000 deaths in the US. Although it has been suggested that adaptive immunity plays an important role in improving clinical outcomes of patients infected with SARS2, correlates of protective immune responses have not been defined. Also, an explanation for the variability in clinical disease and outcome in patients with SARS2 infection has not been explained based on qualitative and quantitative antiviral immune responses. Studies in immunocompromised adults have shown somewhat decreased efficacy of SARS2 mRNA vaccines and increased rates of breakthrough infections. A significant proportion of children with deficits in immune competence secondary to cancer chemotherapy and hematologic disorders were observed to have blunted antiviral antibody responses following SARS2 infection and shed virus for prolonged periods of time (>6 weeks) in the upper respiratory tract. Together, these findings raise the possibility that children with specific qualitative or quantitative deficits in adaptive immunity may generate somewhat blunted or decreased immune responses to SARS2 vaccines. The safety and immunogenicity of SARS2 mRNA vaccine in young children especially those with compromised immune responses have not been examined. The objective of the proposed study is to define quantitative and qualitative antiviral antibody responses and T cell immunity responses generated following SARS2 mRNA vaccination in a cohort of children with varying levels immune responsiveness and compare those with age-match healthy children. Defining relationships between variations in immune competence and vaccine-mediated protection could provide a novel insight into the level and nature of adaptive immunity that can produce robust immune responses to SARS2 mRNA vaccine. Our studies will also determine the safety of SARS2 mRNA vaccine in children with impaired immunity and in a group of healthy children. Analysis of the quality and quantity of SARS2 antibody and T cell responses to the mRNA vaccine will help develop vaccine candidates or adapt existing vaccines to provide effective protection. In addition, the proposed studies will also examine the durability of vaccine-mediated immunity and the need for additional doses that can protect this vulnerable group of children.