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-Structure paper
タイトル | HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide. |
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ジャーナル・号・ページ | Cell Rep, Vol. 42, Issue 7, Page 112755, Year 2023 |
掲載日 | 2023年7月10日 |
著者 | Shuishu Wang / Flavio Matassoli / Baoshan Zhang / Tracy Liu / Chen-Hsiang Shen / Tatsiana Bylund / Timothy Johnston / Amy R Henry / I-Ting Teng / Prabhanshu Tripathi / Jordan E Becker / Anita Changela / Ridhi Chaudhary / Cheng Cheng / Martin Gaudinski / Jason Gorman / Darcy R Harris / Myungjin Lee / Nicholas C Morano / Laura Novik / Sijy O'Dell / Adam S Olia / Danealle K Parchment / Reda Rawi / Jesmine Roberts-Torres / Tyler Stephens / Yaroslav Tsybovsky / Danyi Wang / David J Van Wazer / Tongqing Zhou / Nicole A Doria-Rose / Richard A Koup / Lawrence Shapiro / Daniel C Douek / Adrian B McDermott / Peter D Kwong / |
PubMed 要旨 | Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers ...Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability. |
リンク | Cell Rep / PubMed:37436899 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.81 - 2.95 Å |
構造データ | EMDB-29725, PDB-8g4m: EMDB-29731, PDB-8g4t: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | ANTIVIRAL PROTEIN / antibody-antigen complex vaccine-elicited antibody fusion peptide strain specific / VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性) |