title: Bystander help within a polyepitope DNA vaccine improves immune responses to influenza antigens.
abstract: A polyepitope DNA vaccine has the potential to generate protective immune responses to a range of antigens in a single construct. We investigated whether it was possible to obtain responses to individual epitopes from different antigens, directly linked in a string, and whether the response to a given epitope was enhanced by adjacent epitopes within the construct. A polyepitope plasmid was created, which included three Th epitopes (influenza haemagglutinin, moth cytochrome c and ovalbumin), a Tc epitope (ovalbumin) and two B cell epitopes (haemagglutinin and ovalbumin). Mice were immunized with DNA by using a gene gun. Responses to the polyepitope DNA vaccine were compared with those to DNA vaccine comprising only the haemagglutinin Th and B epitopes (HAT(h)B) or with responses to the recombinant protein. These experiments showed that the polyepitope DNA vaccine induced greater antigen-specific responses to HAT(h)B peptide than the HAT(h)B DNA vaccine. Antigen-specific in vivo cytotoxic responses following polyepitope DNA vaccination were also clearly demonstrable. We conclude that a 'naked DNA' polyepitope vaccine generates specific responses to constituent epitopes and that adjacent irrelevant epitopes may enhance these responses.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. margaret.baird@stonebow.otago.ac.nz
authors.forename: M
authors.initials: M
authors.lastname: Baird
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.forename: L
authors.initials: L
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Williman
authors.forename: S
authors.initials: S
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.forename: L
authors.initials: L
authors.lastname: Slobbe
authors.forename: E
authors.initials: E
authors.lastname: Lockhart
authors.forename: G
authors.initials: G
authors.lastname: Buchan
mesh_terms: D000818:Animals; D001483:Base Sequence; D019470:Biolistics; D002645:Chickens; D045304:Cytochromes c / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004274:DNA, Recombinant / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009036:Moths; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D004274:DNA, Recombinant; D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015848:Interleukin-5; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D010047:Ovalbumin; D045304:Cytochromes c