EMD-41362
CRYO-EM STRUCTURE OF HIV-1 BG505DS-SOSIP.664 ENV TRIMER BOUND TO HERH-c.01 FAB
EMD-41362
Single-particle3.3 Å
Deposition: 26/07/2023
Map released: 28/08/2024
Last modified: 15/01/2025
Sample Organism:
Human immunodeficiency virus 1,
Homo sapiens
Sample: BG505 DS-SOSIP HERH-c.01 FAB COMPLEX
Fitted models: 8tl5
Deposition Authors: Pletnev S, Hoyt F, Fischer E, Kwong P
Sample: BG505 DS-SOSIP HERH-c.01 FAB COMPLEX
Fitted models: 8tl5
Deposition Authors: Pletnev S, Hoyt F, Fischer E, Kwong P
Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.
Wang H,
Cheng C,
Dal Santo JL,
Shen CH,
Bylund T,
Henry AR,
Howe CA,
Hwang J,
Morano NC,
Morris DJ,
Pletnev S,
Roark RS,
Zhou T,
Hansen BT,
Hoyt FH,
Johnston TS,
Wang S,
Zhang B,
Ambrozak DR,
Becker JE,
Bender MF,
Changela A,
Chaudhary R,
Corcoran M,
Corrigan AR,
Foulds KE,
Guo Y,
Lee M,
Li Y,
Lin BC,
Liu T,
Louder MK,
Mandolesi M,
Mason RD,
McKee K,
Nair V,
O'Dell S,
Olia AS,
Ou L,
Pegu A,
Raju N,
Rawi R,
Roberts-Torres J,
Sarfo EK,
Sastry M,
Schaub AJ,
Schmidt SD,
Schramm CA,
Schwartz CL,
Smith SC,
Stephens T,
Stuckey J,
Teng IT,
Todd JP,
Tsybovsky Y,
Van Wazer DJ,
Wang S,
Doria-Rose NA,
Fischer ER,
Georgiev IS,
Karlsson Hedestam GB,
Sheng Z,
Woodward RA,
Douek DC,
Koup RA,
Pierson TC,
Shapiro L,
Shaw GM,
Mascola JR,
Kwong PD
(2024) Cell , 187 , 7214 - 7231.e23
(2024) Cell , 187 , 7214 - 7231.e23
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 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 [ID50] ∼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 [IC50] < 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.
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 [ID50] ∼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 [IC50] < 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.