6P6F

BG505 SOSIP-I53-50NP

Summary for 6P6F

• Entry DOI: 10.2210/pdb6p6f/pdb
• EMDB information: 20261
• Descriptor: I53-50A.1NT1, I53-50B.4PT1 (2 entities in total)
• Functional Keywords: nanoparticle, self-assembling, hiv, immunogen, sosip
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 117623.59

Authors

Berndsen, Z.T.,Ward, A.B. (deposition date: 2019-06-03, release date: 2019-06-19, Last modification date: 2024-10-30)

Primary citation

Brouwer, P.J.M.,Antanasijevic, A.,Berndsen, Z.,Yasmeen, A.,Fiala, B.,Bijl, T.P.L.,Bontjer, I.,Bale, J.B.,Sheffler, W.,Allen, J.D.,Schorcht, A.,Burger, J.A.,Camacho, M.,Ellis, D.,Cottrell, C.A.,Behrens, A.J.,Catalano, M.,Del Moral-Sanchez, I.,Ketas, T.J.,LaBranche, C.,van Gils, M.J.,Sliepen, K.,Stewart, L.J.,Crispin, M.,Montefiori, D.C.,Baker, D.,Moore, J.P.,Klasse, P.J.,Ward, A.B.,King, N.P.,Sanders, R.W.
Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle.
Nat Commun, 10:4272-4272, 2019

PubMed Abstract: The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

PubMed: 31537780
DOI: 10.1038/s41467-019-12080-1

Experimental method

ELECTRON MICROSCOPY (4.5 Å)