Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes

Jamila Franca Rosengarten; Stefanie Schatz; Tobias Wolf; Stephan Barbe; Jörn Stitz

doi:10.1016/j.virol.2022.01.008

Components of a HIV-1 vaccine mediate virus-like particle (VLP)-formation and display of envelope proteins exposing broadly neutralizing epitopes

Virology. 2022 Mar:568:41-48. doi: 10.1016/j.virol.2022.01.008. Epub 2022 Jan 22.

Authors

Jamila Franca Rosengarten¹, Stefanie Schatz¹, Tobias Wolf², Stephan Barbe³, Jörn Stitz⁴

Affiliations

¹ Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH Köln - University of Applied Sciences, Chempark Leverkusen E28, Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany; Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 5, 30167, Hannover, Germany.
² Research Group Process Engineering, Faculty of Applied Natural Sciences, TH Köln - University of Applied Sciences, Chempark Leverkusen E28, Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany; Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 5, 30167, Hannover, Germany.
³ Research Group Process Engineering, Faculty of Applied Natural Sciences, TH Köln - University of Applied Sciences, Chempark Leverkusen E28, Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany.
⁴ Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH Köln - University of Applied Sciences, Chempark Leverkusen E28, Kaiser-Wilhelm-Allee, 51368, Leverkusen, Germany. Electronic address: joern.stitz@th-koeln.de.

PMID: 35101772
DOI: 10.1016/j.virol.2022.01.008

Abstract

The sequence diversity of HIV-1 is the biggest hurdle for the design of a prophylactic vaccine. Mosaic (Mos) antigens consisting of synthetically shuffled epitopes from various HIV-1 strains are currently tested in the clinical vaccine trial Mosaico (NCT03964415). Besides adenovirus vectors encoding variants of Mos.Gag-Pol and soluble Mos.Env proteins, the Mosaico vaccine entails vectors mediating gene transfer and expression of the membrane-anchored Env-variant Mos2S.Env. We thus examined whether the expression of mosaic Gag mediates the formation of virus-like particles (VLPs). Mos1.Gag- and Mos2.Gag-VLP-formation was readily detected using Western blot- and electron microscopic-analysis. Upon co-expression of both mosaic Gag variants with Mos2S.Env, incorporation of Env into Gag-formed VLPs was observed. The display of the respective neutralization-sensitive target epitopes on Mos2S.Env-decorated VLPs was demonstrated employing a panel of broadly neutralizing antibodies (bNAbs) in a VLP-capture assay. This opens new perspectives for future HIV vaccine designs.

Keywords: Broadly neutralizing antibodies; Mosaic HIV-1 antigens; PiggyBac transposon vectors; Suspension cell lines; Vaccine development; p55-gag virus-like particles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines / immunology*
Antibody Specificity / immunology
Broadly Neutralizing Antibodies / immunology*
Epitopes / genetics
Epitopes / immunology
Gene Order
Genetic Vectors / genetics
HIV Antibodies / immunology*
HIV Infections / immunology*
HIV Infections / prevention & control
HIV-1 / immunology*
Host-Pathogen Interactions
Humans
Vaccines, Virus-Like Particle / immunology*
Vaccines, Virus-Like Particle / ultrastructure
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
Broadly Neutralizing Antibodies
Epitopes
HIV Antibodies
Vaccines, Virus-Like Particle
env Gene Products, Human Immunodeficiency Virus