Fragmentation of SIV-gag Vaccine Induces Broader T Cell Responses

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