title: Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin.
abstract: The rapid genetic drift of influenza virus hemagglutinin is an obstacle to vaccine efficacy. Previously, we found that the consensus hemagglutinin DNA vaccine (pCHA5) can only elicit moderate neutralization activities toward the H5N1 clade 2.1 and clade 2.3 viruses. Two approaches were thus taken to improve the protection broadness of CHA5. The first one was to include certain surface amino acids that are characteristic of clade 2.3 viruses to improve the protection profiles. When we immunized mice with CHA5 harboring individual mutations, the antibodies elicited by CHA5 containing P157S elicited higher neutralizing activity against the clade 2.3 viruses. Likewise, the viruses pseudotyped with hemagglutinin containing 157S became more susceptible to neutralization. The second approach was to update the consensus sequence with more recent H5N1 strains, generating a second-generation DNA vaccine pCHA5II. We showed that pCHA5II was able to elicit higher cross-neutralization activities against all H5N1 viruses. Comparison of the neutralization profiles of CHA5 and CHA5II, and the animal challenge studies, revealed that CHA5II induced the broadest protection profile. We concluded that CHA5II combined with electroporation delivery is a promising strategy to induce antibodies with broad cross-reactivities against divergent H5N1 influenza viruses.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chen
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Liao
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Jia-Tsrong
authors.initials: JT
authors.lastname: Jan
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Chien-Tai
authors.initials: CT
authors.lastname: Ren
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.forename: Ting-Jen Rachel
authors.initials: TJ
authors.lastname: Cheng
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D050260:Carbohydrate Metabolism / Q000276:immunology*; D002460:Cell Line; D056738:Cross Protection / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D011134:Polysaccharides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000596:Amino Acids; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007106:Immune Sera; D007252:Influenza Vaccines; D011134:Polysaccharides; D011991:Receptors, Virus; D019444:Vaccines, DNA