Mathematical Models of Immune Responses to Infectious Diseases
Erwin, Samantha H
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In this dissertation, we investigate the mechanisms behind diseases and the immune responses required for successful disease resolution in three projects: i) A study of HIV and HPV co-infection, ii) A germinal center dynamics model, iii) A study of monoclonal antibody therapy. We predict that the condition leading to HPV persistence during HIV/HPV co-infection is the permissive immune environment created by HIV, rather than the direct HIV/HPV interaction. In the second project, we develop a germinal center model to understand the mechanisms that lead to the formation of potent long-lived plasma. We predict that the T follicular helper cells are a limiting resource and present possible mechanisms that can revert this limitation in the presence of non-mutating and mutating antigen. Finally, we develop a pharmacokinetic model of 3BNC117 antibody dynamics and HIV viral dynamics following antibody therapy. We fit the models to clinical trial data and conclude that antibody binding is delayed and that the combined effects of initial CD4 T cell count, initial HIV levels, and virus production are strong indicators of a good response to antibody immunotherapy.
- Doctoral Dissertations