4OM0

Crystal structure of antibody VRC07-G54Y in complex with clade A/E 93TH057 HIV-1 gp120 core

Summary for 4OM0

• Entry DOI: 10.2210/pdb4om0/pdb
• Related: 4OLU 4OLV 4OLW 4OLX 4OLY 4OLZ 4OM1
• Descriptor: Envelope glycoprotein gp160, Antigen binding fragment of heavy chain: Antibody VRC01, Antigen binding fragment of light chain: Antibody VRC01, ... (5 entities in total)
• Functional Keywords: vrc07 antibody, passive transfer, neutralization, in vivo protection, autoreactivity, lentiviral infection, enhanced potency, hiv-1 gp120, vrc07-g54y, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 89556.43

Authors

Kwon, Y.D.,Kwong, P.D. (deposition date: 2014-01-25, release date: 2014-09-03, Last modification date: 2023-09-20)

Primary citation

Rudicell, R.S.,Kwon, Y.D.,Ko, S.Y.,Pegu, A.,Louder, M.K.,Georgiev, I.S.,Wu, X.,Zhu, J.,Boyington, J.C.,Chen, X.,Shi, W.,Yang, Z.Y.,Doria-Rose, N.A.,McKee, K.,O'Dell, S.,Schmidt, S.D.,Chuang, G.Y.,Druz, A.,Soto, C.,Yang, Y.,Zhang, B.,Zhou, T.,Todd, J.P.,Lloyd, K.E.,Eudailey, J.,Roberts, K.E.,Donald, B.R.,Bailer, R.T.,Ledgerwood, J.,Mullikin, J.C.,Shapiro, L.,Koup, R.A.,Graham, B.S.,Nason, M.C.,Connors, M.,Haynes, B.F.,Rao, S.S.,Roederer, M.,Kwong, P.D.,Mascola, J.R.,Nabel, G.J.
Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo.
J.Virol., 88:12669-12682, 2014

PubMed Abstract: Over the past 5 years, a new generation of highly potent and broadly neutralizing HIV-1 antibodies has been identified. These antibodies can protect against lentiviral infection in nonhuman primates (NHPs), suggesting that passive antibody transfer would prevent HIV-1 transmission in humans. To increase the protective efficacy of such monoclonal antibodies, we employed next-generation sequencing, computational bioinformatics, and structure-guided design to enhance the neutralization potency and breadth of VRC01, an antibody that targets the CD4 binding site of the HIV-1 envelope. One variant, VRC07-523, was 5- to 8-fold more potent than VRC01, neutralized 96% of viruses tested, and displayed minimal autoreactivity. To compare its protective efficacy to that of VRC01 in vivo, we performed a series of simian-human immunodeficiency virus (SHIV) challenge experiments in nonhuman primates and calculated the doses of VRC07-523 and VRC01 that provide 50% protection (EC50). VRC07-523 prevented infection in NHPs at a 5-fold lower concentration than VRC01. These results suggest that increased neutralization potency in vitro correlates with improved protection against infection in vivo, documenting the improved functional efficacy of VRC07-523 and its potential clinical relevance for protecting against HIV-1 infection in humans.

PubMed: 25142607
DOI: 10.1128/JVI.02213-14

Experimental method

X-RAY DIFFRACTION (2.289 Å)