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-Structure paper
タイトル | Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. |
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ジャーナル・号・ページ | Nat Med, Vol. 24, Issue 6, Page 857-867, Year 2018 |
掲載日 | 2018年6月4日 |
著者 | Kai Xu / Priyamvada Acharya / Rui Kong / Cheng Cheng / Gwo-Yu Chuang / Kevin Liu / Mark K Louder / Sijy O'Dell / Reda Rawi / Mallika Sastry / Chen-Hsiang Shen / Baoshan Zhang / Tongqing Zhou / Mangaiarkarasi Asokan / Robert T Bailer / Michael Chambers / Xuejun Chen / Chang W Choi / Venkata P Dandey / Nicole A Doria-Rose / Aliaksandr Druz / Edward T Eng / S Katie Farney / Kathryn E Foulds / Hui Geng / Ivelin S Georgiev / Jason Gorman / Kurt R Hill / Alexander J Jafari / Young D Kwon / Yen-Ting Lai / Thomas Lemmin / Krisha McKee / Tiffany Y Ohr / Li Ou / Dongjun Peng / Ariana P Rowshan / Zizhang Sheng / John-Paul Todd / Yaroslav Tsybovsky / Elise G Viox / Yiran Wang / Hui Wei / Yongping Yang / Amy F Zhou / Rui Chen / Lu Yang / Diana G Scorpio / Adrian B McDermott / Lawrence Shapiro / Bridget Carragher / Clinton S Potter / John R Mascola / Peter D Kwong / |
PubMed 要旨 | 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- ...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. |
リンク | Nat Med / PubMed:29867235 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.55 - 19.6 Å |
構造データ | EMDB-7459, PDB-6cde: EMDB-7460, PDB-6cdi: EMDB-8420: EMDB-8421: EMDB-8422: PDB-5tkj: PDB-5tkk: PDB-6cdm: PDB-6cdo: PDB-6cdp: |
化合物 | ChemComp-SO4: ChemComp-HOH: ChemComp-NAG: ChemComp-MAN: |
由来 |
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キーワード | IMMUNE SYSTEM / Neutralizing / antibody / fusion-peptide / complex / mouse / VIRAL PROTEIN / HIV-1 Env / BG505 SOSIP / fusion peptide / VRC03 / PGT122 / vFP20.01 / vFP16.02 |