Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.

Publication Type:

Journal Article

Source:

Cell, Volume 187, Issue 25, p.7214-7231.e23 (2024)

Keywords:

AIDS Vaccines, Animals, Antibodies, Neutralizing, B-Lymphocytes, Cross Reactions, Cryoelectron Microscopy, HIV Antibodies, HIV Infections, HIV-1, Humans, Macaca, Macaca mulatta, Peptides, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus

Abstract:

<p>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] &sim;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]&nbsp;&lt;&nbsp;50&nbsp;μg/mL) and total lineage-concentrations estimates of 50-200&nbsp;μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in&nbsp;vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.</p>

PDB: 
8TDX, 8TE7, 8TNU, 8TO7, 8TO9
Detector: 
EIGER
Beamline: 
24-ID-E