Unknown

Dataset Information

0

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 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. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight 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. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

SUBMITTER: Steichen JM 

PROVIDER: S-EPMC11309785 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Steichen Jon M JM   Phung Ivy I   Salcedo Eugenia E   Ozorowski Gabriel G   Willis Jordan R JR   Baboo Sabyasachi S   Liguori Alessia A   Cottrell Christopher A CA   Torres Jonathan L JL   Madden Patrick J PJ   Ma Krystal M KM   Sutton Henry J HJ   Lee Jeong Hyun JH   Kalyuzhniy Oleksandr O   Allen Joel D JD   Rodriguez Oscar L OL   Adachi Yumiko Y   Mullen Tina-Marie TM   Georgeson Erik E   Kubitz Michael M   Burns Alison A   Barman Shawn S   Mopuri Rohini R   Metz Amanda A   Altheide Tasha K TK   Diedrich Jolene K JK   Saha Swati S   Shields Kaitlyn K   Schultze Steven E SE   Smith Melissa L ML   Schiffner Torben T   Burton Dennis R DR   Watson Corey T CT   Bosinger Steven E SE   Crispin Max M   Yates John R JR   Paulson James C JC   Ward Andrew B AB   Sok Devin D   Crotty Shane S   Schief William R WR  

Science (New York, N.Y.) 20240517 6697


Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to 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. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precu  ...[more]

Similar Datasets

2024-02-26 | MSV000094174 | MassIVE
| S-EPMC5404394 | biostudies-literature
| S-EPMC9671094 | biostudies-literature
| S-EPMC10860651 | biostudies-literature
| S-EPMC7092357 | biostudies-literature
| S-EPMC11147780 | biostudies-literature
2023-03-11 | PXD033766 | Pride
| S-EPMC5408352 | biostudies-literature
| S-EPMC8049513 | biostudies-literature
| S-EPMC10769253 | biostudies-literature