6DFH

BG505 MD64 N332-GT2 SOSIP trimer in complex with germline-reverted BG18 fragment antigen binding

Summary for 6DFH

• Entry DOI: 10.2210/pdb6dfh/pdb
• Related: 6DFG
• EMDB information: 7875 7876
• Descriptor: Envelope glycoprotein gp160, germline-reverted BG18 fragment antigen binding heavy chain, germline-reverted BG18 fragment antigen binding light chain, ... (8 entities in total)
• Functional Keywords: hiv-1, hiv envelope, sosip, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 12
• Total formula weight: 375572.51

Authors

Ozorowski, G.,Steichen, J.M.,Schief, W.R.,Ward, A.B. (deposition date: 2018-05-14, release date: 2019-11-06, Last modification date: 2020-07-29)

Primary citation

Steichen, J.M.,Lin, Y.C.,Havenar-Daughton, C.,Pecetta, S.,Ozorowski, G.,Willis, J.R.,Toy, L.,Sok, D.,Liguori, A.,Kratochvil, S.,Torres, J.L.,Kalyuzhniy, O.,Melzi, E.,Kulp, D.W.,Raemisch, S.,Hu, X.,Bernard, S.M.,Georgeson, E.,Phelps, N.,Adachi, Y.,Kubitz, M.,Landais, E.,Umotoy, J.,Robinson, A.,Briney, B.,Wilson, I.A.,Burton, D.R.,Ward, A.B.,Crotty, S.,Batista, F.D.,Schief, W.R.
A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.
Science, 366:-, 2019

PubMed Abstract: Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.

PubMed: 31672916
DOI: 10.1126/science.aax4380

Experimental method

ELECTRON MICROSCOPY (3.85 Å)