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

2023; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/s41541-023-00648-4

2059-0105

Ferran Tarrés-Freixas, Carmen Aguilar‐Gurrieri, Maria Luisa Rodrı́guez de la Concepción, Víctor Urrea, Benjamin Trinité, Raquel Ortiz, Edwards Pradenas, Pau Blanco, Sílvia Marfil, Luis M. Molinos‐Albert, Ana Barajas, Anna Pons-Grífols, Carlos Ávila‐Nieto, Ismael Varela, Laura Cervera, Sònia Gutiérrez-Granados, María Mercedes Segura, Francesc Gòdia, Bonaventura Clotet, Jorge Carrillo, Julià Blanco,

Immune Cell Function and Interaction

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.