THE INTERSECTION OF HOST IMMUNITY AND VIRAL EVOLUTION: SPECIFIC AND NON-SPECIFIC HOST IMMUNE PRESSURES HAVE DIFFERENTIAL INFLUENCES ON INFLUENZA VIRUS AND SARS-COV-2 ANTIGENIC CHANGES

Abstract

Improvements to public health strategies surrounding vaccination against mutating respiratory pathogens requires a more in-depth understanding of the host factors driving viral evolution. In this thesis, I used informatic pipelines to investigate the impact of specific host immunity on viral mutation across influenza virus proteins and antigenic differences in the SARS-CoV-2 spike proteins across circulating variants. Using a mouse model of previous influenza virus infection and vaccination, I characterized viral mutations present in the lungs of mice at heterologous challenge and found that strain-specific immune responses facilitated the greatest degree of mutation. My in-silico analysis of SARS-CoV-2 antigenicity suggested changes in B cell epitopes and conservation of T cell epitopes. I propose that the infection and vaccination history of the host dictates the capacity for viral mutation at infection through elicitation of specific immune mechanisms. Additionally, I present an analysis pipeline that could be leveraged in next-generation vaccine design against respiratory viruses.