Online

Strother, Camilla Ann

Cellular, Molecular, and Biomedical Sciences Graduate Program

2023

Ph. D.

This dissertation encompasses original research on adaptive immune responses triggered by natural viral infections caused by NoV and SARS-CoV-2, as well as an exploration of the rash side effect associated with the TV003 DENV vaccine through the detection of viral RNA. Chapter II delves into the adaptive immune response to GII.17 NoV subsequent to infection. Employing a birth cohort study and samples from previously NoV-naïve children, this chapter strives to identify the correlates of protection. Notably, this work has been accepted and is in the press at Frontiers in Immunology.Chapter III is centered on the SARS-CoV-2 pandemic and investigates the memory B cell response in early SARS-CoV-2 cases. Estimations of SARS-CoV-2 reactive memory B cells post-acute infection have led to the isolation of a novel neutralizing mAb. Distinct from most other mAbs examined, which are derived from early non-memory B cell responses, this mAb (Kiplovamab) was generated from a COVID-19 case predating vaccination. Analysis of its neutralization capacity indicates that Kiplovamab may offer valuable insights for identifying crucial immune escape epitopes in emerging SARS-CoV-2 strains. Chapter IV provides insights into the etiology of the rash induced by live attenuated DENV vaccines and challenge viruses. Investigating the presence of viral RNA and the associated inflammatory response in skin biopsies from vaccinated volunteers, this research contributes to understanding the potential connection between rash occurrence and a tetravalent neutralizing antibody response. In summary, this dissertation seeks to address knowledge gaps in the field of immune responses to three distinct RNA viruses, offering insights into the adaptive immune processes triggered by natural viral infections and vaccination, and their implications for the emergence of viral variants.