Dataset Information

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

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.

SUBMITTER: Tarres-Freixas F

PROVIDER: S-EPMC10077320 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Tarrés-Freixas Ferran F Aguilar-Gurrieri Carmen C Rodríguez de la Concepción María Luisa ML Urrea Victor V Trinité Benjamin B Ortiz Raquel R Pradenas Edwards E Blanco Pau P Marfil Sílvia S Molinos-Albert Luis Manuel LM Barajas Ana A Pons-Grífols Anna A Ávila-Nieto Carlos C Varela Ismael I Cervera Laura L Gutiérrez-Granados Sònia S Segura María Mercedes MM Gòdia Francesc F Clotet Bonaventura B Carrillo Jorge J Blanco Julià J

NPJ vaccines 20230406 1

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 resulte ...[more]

PMID: 37024469

Similar Datasets

Project description:BackgroundHigh mutation rates of human immunodeficiency virus (HIV) allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.Methodology/principal findingsthree vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Conclusion/significanceFragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise responses.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets