Self-adjuvanting influenza candidate vaccine presenting epitopes for cell-mediated immunity on a proteinaceous multivalent nanoplatform

Abstract

We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad Dd), for engineering a multivalent vaccination platform carrying influenza epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a proteinaceous, polyvalent, and biodegradable nanoparticle endowed with remarkable endocytosis activity that can be engineered to carry 60 copies of a peptide. Influenza M1 is the most abundant influenza internal protein with the conserved primary structure. Two different M1 immunodominant epitopes were separately inserted in Dd external positions without destroying the particles' dodecahedric structure. Both kinds of DdFluM1 obtained through expression in baculovirus system were properly presented by human dendritic cells triggering efficient activation of antigen-specific T cells responses. Importantly, the candidate vaccine was able to induce cellular immunity in vivo in chickens. These results warrant further investigation of Dd as a platform for candidate vaccine, able to stimulate cellular immune responses.

Keywords: APC; Ad; Ad3; Adenoviral dodecahedron; CTL; Cell-mediated immunity; Dd; FCS; HA; HLA; Influenza vaccine; M1 immunodominant epitopes; MoDC; NA; PBMC; PE; PMA/Iono; Pb; SPF; VLP; Virus-like particle; aa; adenovirus; adenovirus serotype 3; amino acid; antigen-presenting cells; cytotoxic T lymphocyte; dodecahedron; fetal calf serum; hemagglutinin; human leukocyte antigen (a group of the most important antigens responsible for tissue compatibility); monocyte-derived dendritic cells; neuraminidase; pDC; penton base protein; peripheral blood mononuclear cells; phorbol 12-myristate 13-acetate/ionomycin; phycoerythrin; plasmacytoid dendritic cells; recombinant wild-type Dd; rwtDd; specific pathogen-free; virus-like particle.