6P62

HIV Env BG505 NFL TD+ in complex with antibody E70 fragment antigen binding

Summary for 6P62

• Entry DOI: 10.2210/pdb6p62/pdb
• EMDB information: 20259
• Descriptor: HIV-1 Env BG505 NFL TD+, Rabbit monoclonal antibody E70 heavy chain fragment antigen binding, Rabbit monoclonal antibody E70 kappa chain, ... (7 entities in total)
• Functional Keywords: hiv-1, cd4 binding site, neutralizing antibody, rabbit antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 9
• Total formula weight: 379434.71

Authors

Ozorowski, G.,Torres, J.L.,Ward, A.B. (deposition date: 2019-05-31, release date: 2019-11-20, Last modification date: 2024-10-23)

Primary citation

Dubrovskaya, V.,Tran, K.,Ozorowski, G.,Guenaga, J.,Wilson, R.,Bale, S.,Cottrell, C.A.,Turner, H.L.,Seabright, G.,O'Dell, S.,Torres, J.L.,Yang, L.,Feng, Y.,Leaman, D.P.,Vazquez Bernat, N.,Liban, T.,Louder, M.,McKee, K.,Bailer, R.T.,Movsesyan, A.,Doria-Rose, N.A.,Pancera, M.,Karlsson Hedestam, G.B.,Zwick, M.B.,Crispin, M.,Mascola, J.R.,Ward, A.B.,Wyatt, R.T.
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability.
Immunity, 51:915-929.e7, 2019

PubMed Abstract: The elicitation of broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer remains a major vaccine challenge. Most cross-conserved protein determinants are occluded by self-N-glycan shielding, limiting B cell recognition of the underlying polypeptide surface. The exceptions to the contiguous glycan shield include the conserved receptor CD4 binding site (CD4bs) and glycoprotein (gp)41 elements proximal to the furin cleavage site. Accordingly, we performed heterologous trimer-liposome prime:boosting in rabbits to drive B cells specific for cross-conserved sites. To preferentially expose the CD4bs to B cells, we eliminated proximal N-glycans while maintaining the native-like state of the cleavage-independent NFL trimers, followed by gradual N-glycan restoration coupled with heterologous boosting. This approach successfully elicited CD4bs-directed, cross-neutralizing Abs, including one targeting a unique glycan-protein epitope and a bNAb (87% breadth) directed to the gp120:gp41 interface, both resolved by high-resolution cryoelectron microscopy. This study provides proof-of-principle immunogenicity toward eliciting bNAbs by vaccination.

PubMed: 31732167
DOI: 10.1016/j.immuni.2019.10.008

Experimental method

ELECTRON MICROSCOPY (3.57 Å)