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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Brouwer PJM,Antanasijevic A,Berndsen Z,Yasmeen A,Fiala B,Bijl TPL,Bontjer I,Bale JB,Sheffler W,Allen JD,Schorcht A,Burger JA,Camacho M,Ellis D,Cottrell CA,Behrens AJ,Catalano M,Del Moral-Sánchez I,Ketas TJ,LaBranchedoi
10.1038/s41467-019-12080-1subject
Has Abstractpub_date
2019-09-19 00:00:00pages
4272issue
1issn
2041-1723pii
10.1038/s41467-019-12080-1journal_volume
10pub_type
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