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 Cited by 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: 38753769DOI: 10.1126/science.adj8321 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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