EMD-7459
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
EMD-7459
Single-particle3.8 Å
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Map released: 16/05/2018
Last modified: 25/12/2024
Sample Organism:
Homo sapiens,
Human immunodeficiency virus 1
Sample: vFP20.01-BG505 DS-SOSIP-VRC03-PGT122
Fitted models: 6cde (Avg. Q-score: 0.443)
Deposition Authors: Acharya P
,
Carragher B,
Potter CS,
Kwong PD
Sample: vFP20.01-BG505 DS-SOSIP-VRC03-PGT122
Fitted models: 6cde (Avg. Q-score: 0.443)
Deposition Authors: Acharya P
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Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1.
Xu K,
Acharya P
,
Kong R,
Cheng C,
Chuang GY,
Liu K
,
Louder MK
,
O'Dell S,
Rawi R,
Sastry M,
Shen CH,
Zhang B,
Zhou T,
Asokan M
,
Bailer RT,
Chambers M,
Chen X,
Choi CW,
Dandey VP,
Doria-Rose NA,
Druz A,
Eng ET
,
Farney SK,
Foulds KE,
Geng H,
Georgiev IS,
Gorman J
,
Hill KR,
Jafari AJ,
Kwon YD,
Lai YT
,
Lemmin T
,
McKee K,
Ohr TY,
Ou L,
Peng D,
Rowshan AP,
Sheng Z
,
Todd JP,
Tsybovsky Y,
Viox EG,
Wang Y,
Wei H,
Yang Y,
Zhou AF,
Chen R,
Yang L,
Scorpio DG,
McDermott AB
,
Shapiro L,
Carragher B,
Potter CS,
Mascola JR,
Kwong PD
(2018) Nat Med , 24 , 857 - 867
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(2018) Nat Med , 24 , 857 - 867
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.
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.