National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
米国
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ジャーナル: Cell / 年: 2024 タイトル: Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques. 著者: Hua Wang / Cheng Cheng / James L Dal Santo / Chen-Hsiang Shen / Tatsiana Bylund / Amy R Henry / Colin A Howe / Juyun Hwang / Nicholas C Morano / Daniel J Morris / Sergei Pletnev / Ryan S ...著者: Hua Wang / Cheng Cheng / James L Dal Santo / Chen-Hsiang Shen / Tatsiana Bylund / Amy R Henry / Colin A Howe / Juyun Hwang / Nicholas C Morano / Daniel J Morris / Sergei Pletnev / Ryan S Roark / Tongqing Zhou / Bryan T Hansen / Forrest H Hoyt / Timothy S Johnston / Shuyi Wang / Baoshan Zhang / David R Ambrozak / Jordan E Becker / Michael F Bender / Anita Changela / Ridhi Chaudhary / Martin Corcoran / Angela R Corrigan / Kathryn E Foulds / Yicheng Guo / Myungjin Lee / Yingying Li / Bob C Lin / Tracy Liu / Mark K Louder / Marco Mandolesi / Rosemarie D Mason / Krisha McKee / Vinod Nair / Sijy O'Dell / Adam S Olia / Li Ou / Amarendra Pegu / Nagarajan Raju / Reda Rawi / Jesmine Roberts-Torres / Edward K Sarfo / Mallika Sastry / Andrew J Schaub / Stephen D Schmidt / Chaim A Schramm / Cindi L Schwartz / Sarah C Smith / Tyler Stephens / Jonathan Stuckey / I-Ting Teng / John-Paul Todd / Yaroslav Tsybovsky / David J Van Wazer / Shuishu Wang / Nicole A Doria-Rose / Elizabeth R Fischer / Ivelin S Georgiev / Gunilla B Karlsson Hedestam / Zizhang Sheng / Ruth A Woodward / Daniel C Douek / Richard A Koup / Theodore C Pierson / Lawrence Shapiro / George M Shaw / John R Mascola / Peter D Kwong / 要旨: An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the ...An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%-60% (50% inhibitory concentration [IC] < 50 μg/mL) and total lineage-concentrations estimates of 50-200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.