Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination.
It has been difficult to translate promising results from DNA vaccination in mice to larger animals and humans. Previously, DNA vaccines encoding proteins that target Ag to MHC class II (MHC-II) molecules on APCs have been shown to induce rapid, enhanced, and long-lasting Ag-specific Ab titers in mice. In this study, we describe two novel DNA vaccines that as proteins target HLA class II (HLA-II) molecules. These vaccine proteins cross-react with MHC-II molecules in several species of larger mammals. When tested in ferrets and pigs, a single DNA delivery with low doses of the HLA-II-targeted vaccines resulted in rapid and increased Ab responses. Importantly, painless intradermal jet delivery of DNA was as effective as delivery by needle injection followed by electroporation. As an indication that the vaccines could also be useful for human application, HLA-II-targeted vaccine proteins were found to increase human CD4+T cell responses by a factor of ×103in vitro. Thus, targeting of Ag to MHC-II molecules may represent an attractive strategy for increasing efficacy of DNA vaccines in larger animals and humans.
K.G. Jebsen Center for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway; gunnveig.grodeland@medisin.uio.no bjarne.bogen@medisin.uio.no.
Gunnveig
G
Grodeland
Vaccibody AS, 0349 Oslo, Norway.
Agnete Brunsvik
AB
Fredriksen
Center for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway.|Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
Geir Åge
0000-0002-5257-8571
GÅ
Løset
K.G. Jebsen Center for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway.
Elisabeth
0000-0002-7066-3446
E
Vikse
Institute of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark; and.|Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology and Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Lars
0000-0003-2883-3226
L
Fugger
K.G. Jebsen Center for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway; gunnveig.grodeland@medisin.uio.no bjarne.bogen@medisin.uio.no.|Center for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway.
Bjarne
B
Bogen
D000818:Animals; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003429:Cross Reactions; D005289:Ferrets; D006680:HLA Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D013552:Swine; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000941:Antigens; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D019444:Vaccines, DNA
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