Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect

J Infect Dis. 2013 Aug 1;208(3):418-22. doi: 10.1093/infdis/jit180. Epub 2013 Apr 30.


Background: H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV.

Methods: We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks).

Results: H5 DNA priming with an MIV boost ≥12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141-206), compared with 55%-70% of recipients with an H5 DNA and MIV prime-boost interval of ≤8 weeks (GMT, 51-70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27).

Conclusion: H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks. Clinical Trials Registration. NCT01086657.

Keywords: Avian influenza; DNA vaccine; H5N1; boost interval; hemagglutination inhibition.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Female
  • Hemagglutination Inhibition Tests
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunization, Secondary / methods*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Male
  • Middle Aged
  • Time Factors
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology
  • Young Adult


  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Vaccines, DNA
  • Vaccines, Inactivated
  • hemagglutinin, avian influenza A virus

Associated data