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

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606) Human Immunodeficiency Virus (ncbitaxon:12721)

SUBMITTER: John R. Yates III

PROVIDER: MSV000094174 | MassIVE | Mon Feb 26 16:30:00 GMT 2024

SECONDARY ACCESSION(S): PXD050163

REPOSITORIES: MassIVE

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