8G8A

Crystal structure of DH1317.8 Fab in complex with HIV proximal MPER peptide

Summary for 8G8A

• Entry DOI: 10.2210/pdb8g8a/pdb
• Related: 8G8C 8G8D
• Descriptor: DH1317.8 heavy chain, DH1317.8 light chain, Env polyprotein, ... (6 entities in total)
• Functional Keywords: hiv, neutralizing antibody, mper, gp41, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 100760.05

Authors

Janus, B.M.,Astavans, A.,Ofek, G. (deposition date: 2023-02-17, release date: 2024-05-22, Last modification date: 2024-10-16)

Primary citation

Williams, W.B.,Alam, S.M.,Ofek, G.,Erdmann, N.,Montefiori, D.C.,Seaman, M.S.,Wagh, K.,Korber, B.,Edwards, R.J.,Mansouri, K.,Eaton, A.,Cain, D.W.,Martin, M.,Hwang, J.,Arus-Altuz, A.,Lu, X.,Cai, F.,Jamieson, N.,Parks, R.,Barr, M.,Foulger, A.,Anasti, K.,Patel, P.,Sammour, S.,Parsons, R.J.,Huang, X.,Lindenberger, J.,Fetics, S.,Janowska, K.,Niyongabo, A.,Janus, B.M.,Astavans, A.,Fox, C.B.,Mohanty, I.,Evangelous, T.,Chen, Y.,Berry, M.,Kirshner, H.,Van Itallie, E.,Saunders, K.O.,Wiehe, K.,Cohen, K.W.,McElrath, M.J.,Corey, L.,Acharya, P.,Walsh, S.R.,Baden, L.R.,Haynes, B.F.
Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.
Cell, 187:2919-2934.e20, 2024

PubMed Abstract: A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.

PubMed: 38761800
DOI: 10.1016/j.cell.2024.04.033

Experimental method

X-RAY DIFFRACTION (2.44 Å)