| The role of antibodies in controlling HIV infection is still under scrutiny even after more than 25 years of HIV research. Its role in mother-to-child transmission has been especially difficult to discern due to the complexity of isolating the contribution of multiple factors. Because HIV-infected mothers transfer IgG to infants late in gestation, perinatal infection often occurs in the presence of HIV-specific antibodies. Yet little is understood regarding the influence of non-sterilizing levels of preexisting maternal antibodies on the establishment and control of perinatal infection. Therefore, the goal of this dissertation was to determine the role of HIV-specific binding and neutralizing IgG on the development of neutralizing antibodies and the rate of disease progression in neonates. To examine this, I used a macaque model to recapitulate maternal antibodies in perinatal infection. Newborn macaques were given one of three passive treatments: (1) control IgG; (2) IgG with neutralizing activity restricted to SHIVSF162P3; or (3) IgG with neutralizing activity restricted to the heterologous isolate SHIV89.6P . Doses of IgG, below levels that block infection, were administered to neonates prior to oral exposure to SHIVSH62P3. After infection, I observed that only group that received "matched" neutralizing IgG was able to mount rapid, robust de novo neutralizing antibody responses. This was not due to intrinsic differences in B cell responses, as all groups developed indistinguishable responses to hepatitis B vaccination. The presence of de novo neutralizing antibodies was associated with higher CD4+ T cell levels and decreased plasma viremia.;These findings indicate that maternal neutralizing antibodies can have a significant impact on perinatal infection if they are present at the time of exposure by inducing better long-term viral control. IgG that is non-neutralizing for the virus does not incur any beneficial effects. Furthermore, the data reported in this dissertation suggest that antibodies induced by vaccines must be neutralizing in order to control infection and outline a potential new strategy for controlling infection by augmenting B-cell responses. |
