Effects of intra-uterine HIV exposure on antibody functionality and B cell development
Wellcome Trust
University of Cape Town
Approximately 30% of pregnant women in South Africa are HIV-infected resulting in over 300 000 infants exposed to HIV in utero every year. Rates of infectious mortality are reportedly higher among HIV-exposed uninfected infants (iHEU) compared to HIV-unexposed uninfected infants (iHUU). Studies evaluating the effects of maternal HIV infection on vaccine responses in their respective infants show that iHEU have similar antibody titres as those elicited in iHUU. These results imply efficacious vaccination in iHEU which contradicts the observed higher morbidity and mortality rates in iHEU. Therefore, I hypothesise that exposure to HIV in utero may impact the maturation of B cells leading to production of antibodies with poor Fc functions. Our preliminary analysis revealed altered B cell phenotypes across age in iHEU compared to iHUU. Therefore, in this study I aim to characterise B cell properties such as reduced somatic hypermutation for affinity maturation among iHEU using RNA-sequencing. Furthermore, I will analyse IgG Fc glycosylation that is associated with Fc-FcR affinity and Fc effector functions. Subsequently, I will develop in vitro models to measure antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC) specific to early childhood vaccines.
2.1 Biological and endogenous factors