Envelope-specific IgG Responses in HIV-infected Women

Abstract

A better understanding of 1) maternal HIV Envelope (Env)-specific IgG responses that are partially protective against vertical HIV transmission, and 2) factors that mediate the transplacental transfer of maternal protective IgG is needed to improve infant health in early life, in which maternal passively-acquired IgG mediates protection against neonatal infections. To understand maternal factors and IgG characteristics that mediate transplacental IgG transfer, we examined transplacental transfer efficiency determinants of maternal HIV and standard vaccine-antigen-specific IgG in a population of HIV-infected women, which have disrupted transplacental IgG transfer. Our findings suggest that maternal health factors and maternal IgG characteristics, such as binding to placentally expressed Fc receptors, IgG subclass frequency, and Fc region glycan profiles all mediate transplacental IgG transfer efficiency. We also identified maternal linear variable loop 3 (V3)-specific IgG binding and neutralizing responses targeting the C terminal region as partially protective against vertical transmission of HIV. These novel findings provide a roadmap of maternal factors and IgG characteristics as targets that can be harnessed to improve the transplacental IgG transfer of routinely-administered maternal vaccines and benchmarks for assessing maternal HIV vaccines that target the V3 loop.