+Search query
-Structure paper
Title | Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques. |
---|---|
Journal, issue, pages | Cell, Vol. 187, Issue 25, Page 7214-7231.e23, Year 2024 |
Publish date | Dec 12, 2024 |
![]() | 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 / ![]() ![]() |
PubMed Abstract | 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. |
![]() | ![]() ![]() ![]() |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.09 - 4.03 Å |
Structure data | EMDB-41309: CRYO-EM STRUCTURE OF HIV-1 BG505DS-SOSIP.664 ENV TRIMER BOUND TO HERH-c.01 FAB EMDB-41310, PDB-8tjs: EMDB-41346, PDB-8tkc: EMDB-41359, PDB-8tl2: EMDB-41360, PDB-8tl3: EMDB-41361, PDB-8tl4: EMDB-41362, PDB-8tl5: EMDB-41426, PDB-8tnu: EMDB-41438, PDB-8to7: EMDB-41440, PDB-8to9: EMDB-41459, PDB-8top: ![]() PDB-8tdx: ![]() PDB-8te7: |
Chemicals | ![]() ChemComp-HOH: ![]() ChemComp-NAG: |
Source |
|
![]() | IMMUNE SYSTEM / HIV-1 / Fusion Peptide / Antibody / Fab / CD4 Binding Site / Viral Protein/Immune System / SHIV / Viral Protein-Immune System complex / broadly neutralizing antibody / glycoprotein / viral protein / FP-targeting vaccines / Vaccination / HIV-1 Envelope / GPZ6-b.01 / BG505 DS-SOSIP / neutralization / immunization |