"Fc-Mediated Antibody Responses in HIV-1 Mother-to-Child Transmission"
One goal of an HIV-1 vaccine is to elicit antibodies that protect against infection by either neutralizing virus or killing infected cells. At this time, data on the immune correlates of protections from human vaccine trials is limited. Mother-to-child transmission, however, provides another unique setting in which to study the role of pre-existing antibodies in protection. Infants receive passively transferred HIV-specific antibodies in utero that may protect against infection during breastfeeding. This proposal utilizes a unique cohort of 100 HIV-positive mothers and their infants who were uninfected at birth but continually exposed to the virus via breastfeeding. In this cohort, we are interested in studying the role of Fc-mediated antibody responses in protection. One such response is antibody-dependent cellular cytotoxicity (ADCC), which has been shown to influence HIV-1 acquisition and disease progression in macaques. This study will address the hypothesis that passively transferred antibodies capable of mediating ADCC are correlated with risk of infection in infants born to HIV-positive mothers. As ADCC activity is mediated through the Fc portion of the antibody and Fc receptor (FcR) genotype correlates with differential antibody binding, we will also examine the role of FcR genotype on disease acquisition and progression. These studies will provide knowledge on the role of pre-existing ADCC antibodies in preventing HIV acquisition and will help inform future vaccine studies. Furthermore, the FcR genotype data in conjunction with the ADCC analysis will provide insight into host responses that may influence vaccine effectiveness.