8T4A

MD65 N332-GT5 SOSIP in complex with RM_N332_36 Fab and RM20A3 Fab

Summary for 8T4A

• Entry DOI: 10.2210/pdb8t4a/pdb
• EMDB information: 41025
• Descriptor: MD65 N332-GT5 SOSIP gp120, RM20A3 heavy chain Fv, RM20A3 light chain Fv, ... (9 entities in total)
• Functional Keywords: germline targeting, nhp, sosip, env, hiv, bg18, immunogen design, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 18
• Total formula weight: 390816.84

Authors

Ozorowski, G.,Torres, J.L.,Ward, A.B. (deposition date: 2023-06-08, release date: 2024-05-08, Last modification date: 2025-05-14)

Primary citation

Steichen, J.M.,Phung, I.,Salcedo, E.,Ozorowski, G.,Willis, J.R.,Baboo, S.,Liguori, A.,Cottrell, C.A.,Torres, J.L.,Madden, P.J.,Ma, K.M.,Sutton, H.J.,Lee, J.H.,Kalyuzhniy, O.,Allen, J.D.,Rodriguez, O.L.,Adachi, Y.,Mullen, T.M.,Georgeson, E.,Kubitz, M.,Burns, A.,Barman, S.,Mopuri, R.,Metz, A.,Altheide, T.K.,Diedrich, J.K.,Saha, S.,Shields, K.,Schultze, S.E.,Smith, M.L.,Schiffner, T.,Burton, D.R.,Watson, C.T.,Bosinger, S.E.,Crispin, M.,Yates 3rd, J.R.,Paulson, J.C.,Ward, A.B.,Sok, D.,Crotty, S.,Schief, W.R.
Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates.
Science, 384:eadj8321-eadj8321, 2024

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 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.

PubMed: 38753769
DOI: 10.1126/science.adj8321

Experimental method

ELECTRON MICROSCOPY (3.4 Å)