title: Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins.
abstract: Cross-protection between different subtypes of influenza A virus has been attributed to heterosubtypic immunity (HSI). Although, HSI can occur in the absence of anti-HA or anti-NA antibodies, HSI seems to be mediated, in part, by cross-reactive antibodies. In this study, we examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine C3d of complement (HA-mC3d(3)). HA-mC3d(3) elicited heterosubtypic immunity more efficiently than non-fused forms of HA and protected mice from lethal challenge of influenza with different subtypes. Plasmid encoding for various forms of HA were constructed from two influenza strains, A/Puerto Rico/8/34 (H1N1) or A/Aichi/2/68-x31 (H3N2). Vaccinated mice were analyzed for enhancement of anti-HA titers, affinity maturation of antibody, hemagglutinin-inhibition activity, and altered cytokine profiles. The HA-mC3d(3)-DNA vaccinated mice were protected from heterologous influenza challenge, even though sera from these mice had no viral-neutralizing activity against heterologous virus.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, East Carolina University, Brody Health Sciences Building, Room 5N/96E, 600 Moye Boulevard, Greenville, NC 27858-4354, USA.
authors.forename: Judy A
authors.initials: JA
authors.lastname: Mitchell
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Green
authors.forename: Rick A
authors.initials: RA
authors.lastname: Bright
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002460:Cell Line; D015933:Complement C3d / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics* / Q000494:pharmacology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000235:genetics* / Q000494:pharmacology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015933:Complement C3d