8SWV

BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody IF1

Summary for 8SWV

• Entry DOI: 10.2210/pdb8swv/pdb
• Related: 8T2E
• EMDB information: 40822
• Descriptor: Surface protein gp120, Transmembrane protein gp41, IF1 Heavy Chain, ... (8 entities in total)
• Functional Keywords: hiv-1, env, nhp, antibody, fusion peptide, polyclonal, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 8
• Total formula weight: 258599.61

Authors

Pratap, P.P.,Antansijevic, A.,Ozorowski, G.,Ward, A.B. (deposition date: 2023-05-19, release date: 2024-05-22, Last modification date: 2024-10-09)

Primary citation

Cottrell, C.A.,Pratap, P.P.,Cirelli, K.M.,Carnathan, D.G.,Enemuo, C.A.,Antanasijevic, A.,Ozorowski, G.,Sewall, L.M.,Gao, H.,Allen, J.D.,Nogal, B.,Silva, M.,Bhiman, J.,Pauthner, M.,Irvine, D.J.,Montefiori, D.,Crispin, M.,Burton, D.R.,Silvestri, G.,Crotty, S.,Ward, A.B.
Priming antibody responses to the fusion peptide in rhesus macaques.
Npj Vaccines, 9:126-126, 2024

PubMed Abstract: Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.

PubMed: 38997302
DOI: 10.1038/s41541-024-00918-9

Experimental method

ELECTRON MICROSCOPY (3.37 Å)