An engineered HIV-1 Gag-based VLP displaying high antigen density induces strong antibody-dependent functional immune responses

Ana Barajas Vélez, Laura Cervera Gracia, Francesc Gòdia, Bonaventura Clotet Sala, Ferran Tarrés-Freixas, Carmen Aguilar-Gurrieri, María Luisa Rodríguez de la Concepción, Víctor Urrea, Benjamin Trinité, Raquel Ortiz, Edwards Pradenas, Pau Blanco, Sílvia Marfil, Luis Manuel Molinos-Albert, Anna Pons-Grífols, Carlos Avila-Nieto, Ismael Varela, Sònia Gutiérrez-Granados, María Mercedes Segura, Jorge CarrilloJulià Blanco

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Antigen display on the surface of Virus-Like Particles (VLPs) improves immunogenicity compared to soluble proteins. We hypothesised that immune responses can be further improved by increasing the antigen density on the surface of VLPs. In this work, we report an HIV-1 Gag-based VLP platform engineered to maximise the presence of antigen on the VLP surface. An HIV-1 gp41-derived protein (Min), including the C-terminal part of gp41 and the transmembrane domain, was fused to HIV-1 Gag. This resulted in high-density MinGag-VLPs. These VLPs demonstrated to be highly immunogenic in animal models using either a homologous (VLP) or heterologous (DNA/VLP) vaccination regimen, with the latter yielding 10-fold higher anti-Gag and anti-Min antibody titres. Despite these strong humoral responses, immunisation with MinGag-VLPs did not induce neutralising antibodies. Nevertheless, antibodies were predominantly of an IgG2b/IgG2c profile and could efficiently bind CD16-2. Furthermore, we demonstrated that MinGag-VLP vaccination could mediate a functional effect and halt the progression of a Min-expressing tumour cell line in an in vivo mouse model.
Original languageEnglish
Article number51
Journalnpj Vaccines
Volume8
Issue number1
DOIs
Publication statusPublished - 6 Apr 2023

Keywords

  • Antibodies
  • DNA vaccines
  • HIV infections
  • Protein vaccines
  • Retrovirus

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