Electronic Thesis/Dissertation
 

Strategies to Utilize Antibodies for HIV-1 Treatment and Prevention

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Currently there is no effective vaccine against HIV-1, and treatment strategies typically rely on daily therapies that allow rapid viral rebound if interrupted. Improvements to both treatment and prevention strategies are high priorities given the major global burden that HIV-1 represents. Here, we examine potential improvements to therapies for both treatment of HIV-1 infection and prevention of viral acquisition. First, we investigated treatment strategies by sequencing outgrowth viruses from individuals stably treated on antiretroviral therapy (ART) and assessing the susceptibility of these viruses to neutralization by broadly neutralizing antibodies (bnAbs) and autologous IgG. We observed that individuals with greater env gene diversity in their latent reservoirs were on average more resistant to bnAbs, and that all outgrowth viruses were fairly resistant to autologous neutralization. Secondly, we examined the impact of oral probiotic adjuvants on SHIV vaccination in a macaque model. We observed that probiotic treatments alongside vaccination significantly reduced circulating IgA titers during subsequent SHIV infection, but did not impact circulating anti-commensal antibody titers. By investigating approaches to better utilize antibodies in treatment and prevention strategies, we hope to advance the critical field of HIV-1 medicine.

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