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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 ×103 in 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.

Original publication

DOI

10.4049/jimmunol.1600893

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

11/2016

Volume

197

Pages

3575 - 3585

Addresses

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.

Keywords

Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, Cells, Cultured, Animals, Swine, Ferrets, Humans, Mice, Vaccines, DNA, Antigens, Histocompatibility Antigens Class II, HLA Antigens, Vaccination, Lymphocyte Activation, Cell Proliferation, Antibody Formation, Cross Reactions