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

Autor: Tarrés-Freixas F; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Aguilar-Gurrieri C; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Rodríguez de la Concepción ML; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Urrea V; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Trinité B; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Ortiz R; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Pradenas E; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Blanco P; Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Marfil S; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Molinos-Albert LM; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain.; ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain., Barajas A; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Pons-Grífols A; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Ávila-Nieto C; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Varela I; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain., Cervera L; Grup d'Enginyeria Cel•lular i Bioprocessos, Department of Chemical, Biological and Environmental Engineering, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08913, Cerdanyola del Vallès, Catalonia, Spain., Gutiérrez-Granados S; Grup d'Enginyeria Cel•lular i Bioprocessos, Department of Chemical, Biological and Environmental Engineering, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08913, Cerdanyola del Vallès, Catalonia, Spain., Segura MM; Grup d'Enginyeria Cel•lular i Bioprocessos, Department of Chemical, Biological and Environmental Engineering, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08913, Cerdanyola del Vallès, Catalonia, Spain., Gòdia F; Grup d'Enginyeria Cel•lular i Bioprocessos, Department of Chemical, Biological and Environmental Engineering, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, 08913, Cerdanyola del Vallès, Catalonia, Spain., Clotet B; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain.; University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Barcelona, Spain., Carrillo J; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain. jcarrillo@irsicaixa.es.; Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, 08916, Barcelona, Spain. jcarrillo@irsicaixa.es.; CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. jcarrillo@irsicaixa.es., Blanco J; IrsiCaixa AIDS Research Institute, Can Ruti Campus, 08916, Badalona, Catalonia, Spain. jblanco@irsicaixa.es.; University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Barcelona, Spain. jblanco@irsicaixa.es.; Germans Trias i Pujol Research Institute (IGTP), Can Ruti Campus, Badalona, 08916, Barcelona, Spain. jblanco@irsicaixa.es.; CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. jblanco@irsicaixa.es.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2023 Apr 06; Vol. 8 (1), pp. 51. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1038/s41541-023-00648-4
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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