title: Efficient vaccine against pandemic influenza: combining DNA vaccination and targeted delivery to MHC class II molecules.
abstract: There are two major limitations to vaccine preparedness in the event of devastating influenza pandemics: the time needed to generate a vaccine and rapid generation of sufficient amounts. DNA vaccination could represent a solution to these problems, but efficacy needs to be enhanced. In a separate line of research, it has been established that targeting of vaccine molecules to antigen-presenting cells enhances immune responses. We have combined the two principles by constructing DNA vaccines that encode bivalent fusion proteins; these target hemagglutinin to MHC class II molecules on antigen-presenting cells. Such DNA vaccines rapidly induce hemagglutinin-specific antibodies and T cell responses in immunized mice. Responses are long-lasting and protect mice against challenge with influenza virus. In a pandemic situation, targeted DNA vaccines could be produced and tested within a month. The novel DNA vaccines could represent a solution to pandemic preparedness in the advent of novel influenza pandemics.
authors.affiliation: Institute of Immunology, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0027 Oslo, Norway.
authors.forename: Gunnveig
authors.initials: G
authors.lastname: Grødeland
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D055808:Drug Discovery / Q000639:trends; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000517:prevention & control*; D058873:Pandemics / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D019444:Vaccines, DNA
keywords: APC targeting; DNA vaccine; MHC II molecules; antibodies; influenza; vaccine