title: DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial.
abstract: BACKGROUND
  The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.
  
  
  METHODS
  Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective.
  
  
  RESULTS
  The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.
  
  
  CONCLUSIONS
  While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01498718.
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.affiliation: The EMMES Corporation, Rockville, Maryland, United States of America.
authors.forename: Abbie R
authors.initials: AR
authors.lastname: Bellamy
authors.affiliation: Edward A. Daisy Research Center, Saint Louis University, Saint Louis, Missouri, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Belshe
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.affiliation: Department of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine Houston, Texas, United States of America.
authors.forename: Shital M
authors.initials: SM
authors.lastname: Patel
authors.affiliation: The EMMES Corporation, Rockville, Maryland, United States of America.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Renehan
authors.affiliation: The EMMES Corporation, Rockville, Maryland, United States of America.
authors.forename: Thad
authors.initials: T
authors.lastname: Zajdowicz
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Schwartz
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Koup
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Yamshchikov
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Uzma
authors.initials: U
authors.lastname: Sarwar
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Brenda
authors.initials: B
authors.lastname: Larkin
authors.affiliation: Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000276:immunology; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated