Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles | Zendy

Linling He | Zendy; Natalia de Val | Zendy; Charles D. Morris | Zendy; Nemil Vora | Zendy; T Thinnes | Zendy; Leopold Kong | Zendy; P. Azadnia | Zendy; Devin Sok | Zendy; Bin Zhou | Zendy; Dennis R. Burton | Zendy; Ian A. Wilson | Zendy; David Nemazee | Zendy; Andrew B. Ward | Zendy; Jiang Zhu | Zendy

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Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles

Author(s) -

Linling He,

Natalia de Val,

Charles D. Morris,

Nemil Vora,

T Thinnes,

Leopold Kong,

P. Azadnia,

Devin Sok,

Bin Zhou,

Dennis R. Burton,

Ian A. Wilson,

David Nemazee,

Andrew B. Ward,

Jiang Zhu

Publication year - 2016

Publication title -

nature communications

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.559

H-Index - 365

ISSN - 2041-1723

DOI - 10.1038/ncomms12041

Subject(s) - trimer , context (archaeology) , antigen , nanoparticle , virus like particle , chemistry , antibody , human immunodeficiency virus (hiv) , microbiology and biotechnology , hiv vaccine , virology , biophysics , biology , nanotechnology , materials science , immunology , recombinant dna , biochemistry , vaccine trial , paleontology , dimer , organic chemistry , gene

Structures of BG505 SOSIP.664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles. We then design nanoparticles presenting various forms of stabilized gp140 trimer based on ferritin and a large, 60-meric E2p that displays 20 spikes mimicking virus-like particles (VLPs). Particle assembly is confirmed by electron microscopy (EM), while antigenic profiles are generated using representative bNAbs and non-NAbs. Lastly, we demonstrate high-yield gp140 nanoparticle production and robust stimulation of B cells carrying cognate VRC01 receptors by gp120 and gp140 nanoparticles. Together, our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development.

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