Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle

By P. Brouwer, A. Antanasijevic, Z. Berndsen, A. Yasmeen, B. Fiala, Tom P. L. Bijl, I. Bontjer, J. Bale, W. Sheffler, Joel D. Allen and 21 more. 2019

177 citations recorded by the source corpus.

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. Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.

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A. Walls
B. Fiala
Seyhan Boyoglu-Barnum
A. Schäfer
K. Dinnon
Samuel P Wrenn
S. Leist
M. Murphy

Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “, 2019), HIV-1 envelope (Brouwer et al., 2019), influenza hemagglutinin (Boyoglu-Barnum et al.”
Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines (2020, background): “Several potential factors may contribute to this effect, such as the geometric relationship between neighboring HAs on the nanoparticle surface 33,42,45 , preferential antigen uptake or retention kinetics by macrophages and follicular dendritic cells 63 , or the presence of T helper epitopes…”