Core C: B Cell Core

ABSTRACT – B Cell Core Early development of bNAbs in infants suggest potentially distinct mechanisms in the generation of antibody breadth due to the highly dynamic nature of the infant immune system. Moreover, we have observed elicitation of bNAb precursors in infant rhesus monkeys with germline-targeting HIV Env SOSIP immunization. We hypothesize that induction of bnAb precursor B cells using germline-targeting HIV Env SOSIP immunogens requires specific innate and microbial interactions which are modifiable to enhance future HIV vaccine strategies, particularly in early life. In this context, we propose a B Cell Core that will perform in-depth quantification and characterization of the plasma and B cell responses after BG505 SOSIP GT1.1 immunizations in infant macaques over time through i) the quantification of the functional activity, avidity and target epitope of polyclonal plasma antibody responses (Aim 1) and ii) single cell RNA sequencing of antigen-specific B cell analysis (Aim 2) to evaluate the evolution of vaccine-elicited HIV bNAb precursors and relate these responses to innate immunity (Project 1) and microbial interactions (Project 2). To accomplish this goal, the B Cell Core will draw on the extensive experience and unique resources in antibody and B cell response characterization of the B Cell Core Leader Dr. Marit van Gils at Amsterdam UMC and Dr. Sallie Permar at Weill Cornell Medicine.