MassIVE MSV000094174

Partial Public PXD050163

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

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Description

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to human immunodeficiency virus (HIV) and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. We found that immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in 8 of 8 rhesus macaques to substantial frequencies, and with diverse lineages, in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. The results demonstrate proof of principle for priming of HCDR3-dominant bnAb precursors in outbred animals, suggest that N332-GT5 has promise to induce similar responses in humans, and encourage application of HCDR3-dominant germline-targeting for other bnAbs to HIV and additional pathogens. [doi:10.25345/C5X921W19] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: DeGlyPHER ; N-glycans ; HIV Env trimer ; vaccine ; germline targeting ; V3-glycan epitope ; bNAb

Contact

Principal Investigators:
(in alphabetical order) 		John R. Yates III, The Scripps Research Institute, USA
Submitting User: sbaboo
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