Scientific Core Two

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PROJECT SUMMARY/ABSTRACT Broadly neutralizing antibodies are likely to be an important component of an HIV-1 vaccine. The HIV-1 Envelope (Env) glycoprotein is the sole target of neutralizing antibodies and has been a focus of immunogen designs. Yet diverse recombinant (rec) Envs do not display detectable binding to the inferred germline (gl) of certain bNAbs, such as the VRC01-class bNAbs, which are the focus of our IPCAVD project. Rec Envs capable of binding glVRC01 bNAbs have been designed and induced the production of glVRC01 bNAbs when used as immunogens. In this IPCAVD, we propose to determine if self-amplifying (sa) mRNA expressing our germline- targeting 426c.Mod.Core prime and HxB2.WT.Core boost immunogens, expressed either as secreted nanoparticles (-C4b) or membrane-anchored (gp160ΔCT), will initiate the maturation of VRC01 B cell response in humans. The Scientific Core Two will provide high quality reagents to Scientific Projects One and Two and Scientific Core One of this IPCAVD as well as structural information on selected vaccine-elicited Mab of interest in complex with their antigens, to delineate their epitopes. This information will help us to better understand the B cell response elicited by the saRNA constructs compared to rec Env immunogens.