7L8W

BG505 SOSIP.v5.2 N241/N289 in complex with the polyclonal Fab pAbC-3 from animal Rh.33311 (Wk26 time point)

Summary for 7L8W

• Entry DOI: 10.2210/pdb7l8w/pdb
• EMDB information: 23176 23236 23237 23238
• Descriptor: BG505 SOSIP.v5.2 N241/N289 - gp120, BG505 SOSIP.v5.2 N241/N289 - gp41, Rh.33311 pAbC-3 - Heavy Chain, ... (8 entities in total)
• Functional Keywords: hiv, vaccine design, bg505, viral protein-immune system complex, polyclonal antibodies, empem, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 8
• Total formula weight: 254874.69

Authors

Antanasijevic, A.,Sewall, L.M.,Ward, A.B. (deposition date: 2021-01-01, release date: 2021-08-04, Last modification date: 2024-10-30)

Primary citation

Antanasijevic, A.,Sewall, L.M.,Cottrell, C.A.,Carnathan, D.G.,Jimenez, L.E.,Ngo, J.T.,Silverman, J.B.,Groschel, B.,Georgeson, E.,Bhiman, J.,Bastidas, R.,LaBranche, C.,Allen, J.D.,Copps, J.,Perrett, H.R.,Rantalainen, K.,Cannac, F.,Yang, Y.R.,de la Pena, A.T.,Rocha, R.F.,Berndsen, Z.T.,Baker, D.,King, N.P.,Sanders, R.W.,Moore, J.P.,Crotty, S.,Crispin, M.,Montefiori, D.C.,Burton, D.R.,Schief, W.R.,Silvestri, G.,Ward, A.B.
Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.
Nat Commun, 12:4817-4817, 2021

PubMed Abstract: Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic.

PubMed: 34376662
DOI: 10.1038/s41467-021-25087-4

Experimental method

ELECTRON MICROSCOPY (4.1 Å)