title: Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin.
abstract: BACKGROUND
  Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches.
  
  
  METHODS
  We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin-adjuvanted plasmid DNA vaccine or placebo 21 days apart. Vaccine cohorts received either a monovalent vaccine containing an A/Vietnam/1203/04 H5 hemagglutinin-encoding plasmid or a trivalent vaccine with plasmids encoding H5, NP, and M2 proteins in doses from 0.1 to 1mg of DNA/injection.
  
  
  RESULTS
  All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of > or =40 and 4-fold rises from baseline were achieved in 47-67% of subjects and H5-specific T-cell responses in 75-100%. Trivalent cohorts had lower HI response rates (< or = 20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens.
  
  
  CONCLUSIONS
  Vaxfectin-adjuvanted monovalent H5 DNA vaccines were well tolerated and induced HI response rates and titers in the reported range of inactivated protein-based H5 vaccines, suggesting that adjuvanted DNA vaccines with rapid vaccine production could be useful for pandemic control.
authors.affiliation: Vical Incorporated, 10390 Pacific Center Court, San Diego, CA 92121, United States. lsmith@vical.com
authors.forename: Larry R
authors.initials: LR
authors.lastname: Smith
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wloch
authors.forename: Ming
authors.initials: M
authors.lastname: Ye
authors.forename: Luane R
authors.initials: LR
authors.lastname: Reyes
authors.forename: Souphaphone
authors.initials: S
authors.lastname: Boutsaboualoy
authors.forename: Casey E
authors.initials: CE
authors.lastname: Dunne
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chaplin
authors.forename: Denis
authors.initials: D
authors.lastname: Rusalov
authors.forename: Alain P
authors.initials: AP
authors.lastname: Rolland
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Fisher
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Al-Ibrahim
authors.forename: Martin L
authors.initials: ML
authors.lastname: Kabongo
authors.forename: Roy
authors.initials: R
authors.lastname: Steigbigel
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
authors.forename: Ernest R
authors.initials: ER
authors.lastname: Kitt
authors.forename: Alice H
authors.initials: AH
authors.lastname: Chu
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moss
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D019590:Nucleocapsid Proteins; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage; D010957:Plasmids; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D010714:Phosphatidylethanolamines; D010919:Placebos; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C048842:NP protein, Influenza A virus; C109963:hemagglutinin, avian influenza A virus; C460866:vaxfectin