Strategies to enhance immunogenicity of cDNA vaccine encoded antigens by modulation of antigen processing

• Published in: Vaccine 2016-09, Vol.34 (42), p.5132-5140
• Main Authors: Platteel, Anouk C.M, Marit de Groot, A, Keller, Christin, Andersen, Peter, Ovaa, Huib, Kloetzel, Peter M, Mishto, Michele, Sijts, Alice J.A.M
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antigen Presentation; Antigens; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; CD8 T cell; CD8-Positive T-Lymphocytes - immunology; Computer Simulation; Deoxyribonucleic acid; Dermal DNA tattoo immunization; DNA; DNA, Complementary; Epitopes, T-Lymphocyte - immunology; Flanking residue optimization; Histocompatibility Antigens Class I - immunology; Immunization; Immunogenicity; Immunogenicity, Vaccine; Lymphocytes; MHC class I-restricted epitopes; Mice; Mycobacterium tuberculosis; Polypeptides; Proteasome; Proteasome Endopeptidase Complex - metabolism; Proteins; Tattoos; Toxins; Tuberculosis Vaccines - immunology; Vaccines; Vaccines, DNA - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2016.08.039

Graphical abstract Vaccine H56 antigen cDNA (1), fused to TTFC (tetanus toxin fragment C) or UB (ubiquitin) cDNA (2) and modified to flank CD8+ T cell epitope’ C-termini with a glutamic acid residue (3) was administered by tattoo immunization. Linkage to either TTFC or UB enhanced CD8+ T cell responses to all epitopes, while replacement of C-terminal epitope flanks for a Glu residue further increased the CD8+ T cell response to 4 out of 6 epitopes. These strategies can be exploited for vaccine design.