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

By Linling He, Natalia de Val, Charles D. Morris, Nemil Vora, Therese C. Thinnes, L. Kong, P. Azadnia, D. Sok, Bin Zhou, D. Burton and 4 more. 2016

171 citations recorded by the source corpus.

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. The development of native-like envelope trimers has been a major focus in the efforts to produce HIV vaccines. Here the authors demonstrate the production and characterization of virus-like nanoparticles displaying trimeric HIV-1 antigens with the potential to elicit broadly neutralizing antibodies.

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging, Virology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. F. Sallusto
2. A. Lanzavecchia
3. Rafi Ahmed
4. Bali Pulendran
5. V. Schirrmacher

In Radiology, Nuclear Medicine and Imaging

1. Neil P. King
2. F. Sallusto
3. David Baker
4. A. Lanzavecchia
5. Frances H. Arnold

In Virology

1. Neil P. King
2. F. Sallusto
3. A. Lanzavecchia

Citations in the corpus

• Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “, 2015), HIV envelope (Abbott et al., 2018; He et al., 2016; Jardine et al., 2015; McGuire et al., 2016; Sliepen et al., 2015), and Epstein-Barr virus (Kanekiyo et al.”
• Development of a Pan-H1 Influenza Vaccine (2018, unknown): “HA (11), EBV gp220 (25), and HIV envelope (26).”