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TitleEnhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 4272, Year 2019
Publish dateSep 19, 2019
AuthorsPhilip J M Brouwer / Aleksandar Antanasijevic / Zachary Berndsen / Anila Yasmeen / Brooke Fiala / Tom P L Bijl / Ilja Bontjer / Jacob B Bale / William Sheffler / Joel D Allen / Anna Schorcht / Judith A Burger / Miguel Camacho / Daniel Ellis / Christopher A Cottrell / Anna-Janina Behrens / Marco Catalano / Iván Del Moral-Sánchez / Thomas J Ketas / Celia LaBranche / Marit J van Gils / Kwinten Sliepen / Lance J Stewart / Max Crispin / David C Montefiori / David Baker / John P Moore / Per Johan Klasse / Andrew B Ward / Neil P King / Rogier W Sanders /
PubMed AbstractThe 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. ...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.
External linksNat Commun / PubMed:31537780 / PubMed Central
MethodsEM (single particle)
Resolution4.5 Å
Structure data

20261

6p6f

EMDB-20261: Single Particle Electron Cryo-Microscopy Reconstruction of BG505 SOSIP-I53-50NP
PDB-6p6f: BG505 SOSIP-I53-50NP
Method: EM (single particle) / Resolution: 4.5 Å

Source
  • synthetic construct (others)
KeywordsIMMUNOGEN / nanoparticle / self-assembling / HIV / SOSIP

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