6CDE

Cryo-EM structure at 3.8 A resolution of vaccine-elicited antibody vFP20.01 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122

This is a non-PDB format compatible entry.

Summary for 6CDE

• Entry DOI: 10.2210/pdb6cde/pdb
• EMDB information: 7459
• Descriptor: vFP20.01 Heavy Chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (19 entities in total)
• Functional Keywords: hiv-1 env, bg505 sosip, fusion peptide, vrc03, pgt122, vfp20.01, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 24
• Total formula weight: 676543.86

Authors

Acharya, P.,Xu, K.,Liu, K.,Carragher, B.,Potter, C.S.,Kwong, P.D. (deposition date: 2018-02-08, release date: 2018-05-16, Last modification date: 2024-12-25)

Primary citation

Xu, K.,Acharya, P.,Kong, R.,Cheng, C.,Chuang, G.Y.,Liu, K.,Louder, M.K.,O'Dell, S.,Rawi, R.,Sastry, M.,Shen, C.H.,Zhang, B.,Zhou, T.,Asokan, M.,Bailer, R.T.,Chambers, M.,Chen, X.,Choi, C.W.,Dandey, V.P.,Doria-Rose, N.A.,Druz, A.,Eng, E.T.,Farney, S.K.,Foulds, K.E.,Geng, H.,Georgiev, I.S.,Gorman, J.,Hill, K.R.,Jafari, A.J.,Kwon, Y.D.,Lai, Y.T.,Lemmin, T.,McKee, K.,Ohr, T.Y.,Ou, L.,Peng, D.,Rowshan, A.P.,Sheng, Z.,Todd, J.P.,Tsybovsky, Y.,Viox, E.G.,Wang, Y.,Wei, H.,Yang, Y.,Zhou, A.F.,Chen, R.,Yang, L.,Scorpio, D.G.,McDermott, A.B.,Shapiro, L.,Carragher, B.,Potter, C.S.,Mascola, J.R.,Kwong, P.D.
Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1.
Nat. Med., 24:857-867, 2018

PubMed Abstract: A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

PubMed: 29867235
DOI: 10.1038/s41591-018-0042-6

Experimental method

ELECTRON MICROSCOPY (3.8 Å)