title: Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect.
abstract: 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).
  
  
  CONCLUSIONS
  H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks. Clinical Trials Registration. NCT01086657.
authors: Vaccine Research Center, National Institute ofAllergy and Infectious Diseases, National Institutes of Health, Bethesda,MD 20892, USA. ledgerwood@mail.nih.gov
authors: Julie E
authors: JE
authors: Ledgerwood
authors: Kathryn
authors: K
authors: Zephir
authors: Zonghui
authors: Z
authors: Hu
authors: Chih-Jen
authors: CJ
authors: Wei
authors: Leejah
authors: L
authors: Chang
authors: Mary E
authors: ME
authors: Enama
authors: Cynthia S
authors: CS
authors: Hendel
authors: Sandra
authors: S
authors: Sitar
authors: Robert T
authors: RT
authors: Bailer
authors: Richard A
authors: RA
authors: Koup
authors: John R
authors: JR
authors: Mascola
authors: Gary J
authors: GJ
authors: Nabel
authors: Barney S
authors: BS
authors: Graham
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; C109963:hemagglutinin, avian influenza A virus
keywords: Avian influenza; DNA vaccine; H5N1; boost interval; hemagglutination inhibition
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