EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization.
ジャーナル・号・ページ	J Virol, Vol. 97, Issue 5, Page e0160422, Year 2023
掲載日	2023年5月31日
著者	Mallika Sastry / Anita Changela / Jason Gorman / Kai Xu / Gwo-Yu Chuang / Chen-Hsiang Shen / Cheng Cheng / Hui Geng / Sijy O'Dell / Li Ou / Reda Rawi / Mateo Reveiz / Guillaume B E Stewart-Jones / Shuishu Wang / Baoshan Zhang / Tongqing Zhou / Andrea Biju / Michael Chambers / Xuejun Chen / Angela R Corrigan / Bob C Lin / Mark K Louder / Krisha McKee / Alexandra F Nazzari / Adam S Olia / Danealle K Parchment / Edward K Sarfo / Tyler Stephens / Jonathan Stuckey / Yaroslav Tsybovsky / Raffaello Verardi / Yiran Wang / Cheng-Yan Zheng / Yuling Chen / Nicole A Doria-Rose / Adrian B McDermott / John R Mascola / Peter D Kwong /
PubMed 要旨	While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could ...While neutralizing antibodies that target the HIV-1 fusion peptide have been elicited in mice by vaccination, antibodies reported thus far have been from only a single antibody class that could neutralize ~30% of HIV-1 strains. To explore the ability of the murine immune system to generate cross-clade neutralizing antibodies and to investigate how higher breadth and potency might be achieved, we tested 17 prime-boost regimens that utilized diverse fusion peptide-carrier conjugates and HIV-1 envelope trimers with different fusion peptides. We observed priming in mice with fusion peptide-carrier conjugates of variable peptide length to elicit higher neutralizing responses, a result we confirmed in guinea pigs. From vaccinated mice, we isolated 21 antibodies, belonging to 4 distinct classes of fusion peptide-directed antibodies capable of cross-clade neutralization. Top antibodies from each class collectively neutralized over 50% of a 208-strain panel. Structural analyses - both X-ray and cryo-EM - revealed each antibody class to recognize a distinct conformation of fusion peptide and to have a binding pocket capable of accommodating diverse fusion peptides. Murine vaccinations can thus elicit diverse neutralizing antibodies, and altering peptide length during prime can improve the elicitation of cross-clade responses targeting the fusion peptide site of HIV-1 vulnerability. The HIV-1 fusion peptide has been identified as a site for elicitation of broadly neutralizing antibodies, with prior studies demonstrating that priming with fusion peptide-based immunogens and boosting with soluble envelope (Env) trimers can elicit cross-clade HIV-1-neutralizing responses. To improve the neutralizing breadth and potency of fusion peptide-directed responses, we evaluated vaccine regimens that incorporated diverse fusion peptide-conjugates and Env trimers with variation in fusion peptide length and sequence. We found that variation in peptide length during prime elicits enhanced neutralizing responses in mice and guinea pigs. We identified vaccine-elicited murine monoclonal antibodies from distinct classes capable of cross-clade neutralization and of diverse fusion peptide recognition. Our findings lend insight into improved immunogens and regimens for HIV-1 vaccine development.
リンク	J Virol / PubMed:37098956 / PubMed Central
手法	EM (単粒子)
解像度	2.5 - 4.66 Å
構造データ	29396 8fr6 EMDB-29396, PDB-8fr6: Antibody vFP53.02 in complex with HIV-1 envelope trimer BG505 DS-SOSIP 手法: EM (単粒子) / 解像度: 2.5 Å 29836 8g85 EMDB-29836, PDB-8g85: vFP52.02 Fab in complex with BG505 DS-SOSIP Env trimer 手法: EM (単粒子) / 解像度: 3.99 Å 29880 8g9w EMDB-29880, PDB-8g9w: Cryo-EM structure of vFP49.02 Fab in complex with HIV-1 Env BG505 DS-SOSIP.664 (conformation 1) 手法: EM (単粒子) / 解像度: 4.66 Å 29881 8g9x EMDB-29881, PDB-8g9x: Cryo-EM structure of vFP49.02 Fab in complex with HIV-1 Env BG505 DS-SOSIP.664 (conformation 2) 手法: EM (単粒子) / 解像度: 4.46 Å 29882 8g9y EMDB-29882, PDB-8g9y: Cryo-EM structure of vFP49.02 Fab in complex with HIV-1 Env BG505 DS-SOSIP.664 (conformation 3) 手法: EM (単粒子) / 解像度: 4.28 Å 29905 8gas EMDB-29905, PDB-8gas: vFP48.02 Fab in complex with BG505 DS-SOSIP Env trimer 手法: EM (単粒子) / 解像度: 4.04 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン
由来	human immunodeficiency virus 1 (ヒト免疫不全ウイルス) mus musculus (ハツカネズミ)
キーワード	VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / fusion peptide envelope trimer murine antibody vFP1 class / ANTIVIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) / VIRAL PROTEIN (ウイルスタンパク質) / HIV-1 / SOSIP / Vaccine (ワクチン) / IMMUNE SYSTEM (免疫系) / fusion peptide (膜融合タンパク質) / FP / antibody (抗体)