Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodies Barton Haynes, MD- PI Sampa Santra, PhD- Co-Investigator The Duke CHAVD has had two major breakthroughs this year in our ability to use rhesus macaques for the study of vaccine-induced bnAb B cell lineages. The first breakthrough was discovering the rhesus VH gene VH1-105 as the rhesus ortholog of human VH1-46 that is used for the VH1-46 class of CD4 mimicking, CD4 binding site (CD4bs) bnAbs.1 We have recently induced rhesus macaque VH1-105 CD4 mimicking, CD4bs bnAb precursors by immunization with the germline targeting Env, CH505M5 G458Y GNT1-.1 The second breakthrough was discovering the rhesus gene VH7-a*01 as the ortholog of human VH7-4-1*02, the VH used by the MPER bnAbs in HVTN 133.2 In rhesus study 181, the MPER peptide-liposome induced VH7-a*01 antibodies with the same MPER specificity and structure as the VH7-4-1*02 DH1317.4 bnAb. Moreover, we have demonstrated boosting of the previously primed MPER clone with an mRNA encoding the proximal and distal MPER epitopes (called mRNA009). Thus, in this supplement, we are requesting support for 6 NHP studies—two MPER, two CD4 binding site, and two V3 glycan bnAb immunization regimens in macaques—each designed to answer questions that are critical to learning the optimal ways to induce bnAbs. Most of these new NHP studies will use recycled monkeys.