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-Structure paper
Title | Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. |
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Journal, issue, pages | Science, Vol. 384, Issue 6697, Page eadj8321, Year 2024 |
Publish date | May 17, 2024 |
![]() | Jon M Steichen / Ivy Phung / Eugenia Salcedo / Gabriel Ozorowski / Jordan R Willis / Sabyasachi Baboo / Alessia Liguori / Christopher A Cottrell / Jonathan L Torres / Patrick J Madden / Krystal M Ma / Henry J Sutton / Jeong Hyun Lee / Oleksandr Kalyuzhniy / Joel D Allen / Oscar L Rodriguez / Yumiko Adachi / Tina-Marie Mullen / Erik Georgeson / Michael Kubitz / Alison Burns / Shawn Barman / Rohini Mopuri / Amanda Metz / Tasha K Altheide / Jolene K Diedrich / Swati Saha / Kaitlyn Shields / Steven E Schultze / Melissa L Smith / Torben Schiffner / Dennis R Burton / Corey T Watson / Steven E Bosinger / Max Crispin / John R Yates / James C Paulson / Andrew B Ward / Devin Sok / Shane Crotty / William R Schief / ![]() ![]() |
PubMed 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 ...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. |
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Methods | EM (single particle) |
Resolution | 2.6 - 3.5 Å |
Structure data | EMDB-41024, PDB-8t49: EMDB-41025, PDB-8t4a: EMDB-41026, PDB-8t4b: EMDB-41027, PDB-8t4d: EMDB-41034, PDB-8t4k: EMDB-41035, PDB-8t4l: |
Chemicals | ![]() ChemComp-NAG: |
Source |
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![]() | VIRAL PROTEIN/Immune System / germline targeting / NHP / SOSIP / Env / HIV / BG18 / immunogen design / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex |