Human chemokine MIP1α increases efficiency of targeted DNA fusion vaccines.
Efficacy of DNA vaccination has been improved in mice by fusion vaccines targeting antigen to antigen-presenting cells (APC) via chemokine receptors. Here, we aimed at extending this strategy to large animals and humans. Fusion proteins equipped with human MIP1α (LD78β isoform) retained functional activity and conformational correctness of targeting and antigenic units, respectively. Fusion proteins improved responses of cloned human CD4+ T cells, and a two amino acid NH(2)-truncated version of LD78β outperformed full length LD78β-vaccine proteins in vitro. LD78β DNA fusion vaccines induced improved T cell (both CD4+ and CD8+) and antibody responses in mice following plasmid injection and skin electroporation. Finally, LD78β-vaccine proteins bound Rhesus macaque CCR5, setting the stage for targeted DNA immunization in non-human primates.
Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway. pieradelchi.ruffini@virgilio.it
Pier Adelchi
PA
Ruffini
Gunnveig
G
Grødeland
Agnete B
AB
Fredriksen
Bjarne
B
Bogen
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3 / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA