DNA priming prior to inactivated influenza A(H5N1) vaccination expands the antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults

J Infect Dis. 2013 Aug 1;208(3):413-7. doi: 10.1093/infdis/jit178. Epub 2013 Apr 30.

Abstract

DNA priming improves the response to inactivated influenza A(H5N1) vaccination. We compared the immunogenicity of an H5 DNA prime (using strain A/Indonesia/5/2005) followed by an H5N1 monovalent inactivated vaccine boost at 4, 8, 12, 16, or 24 weeks to that of 2 doses of H5N1 monovalent inactivated vaccine in adults. Antibody epitope repertoires were elucidated by genome-fragment phage-display library analysis, and antibody avidities for HA1 and HA2 domains were measured by surface plasmon resonance. H5 DNA priming expanded the H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not the HA2) domain in an interval-dependent manner. Enhanced HA1 binding and avidity after an interval of ≥12 weeks between prime and boost correlated with improved neutralization of homologous and heterologous H5N1 strains. Clinical trials registration NCT01086657.

Keywords: H5N1; Phage display; SPR; affinity; antibody; epitope; hemagglutinin; immune response; influenza; vaccine; virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • Antibody Affinity
  • Epitopes / immunology
  • Female
  • Humans
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Male
  • Middle Aged
  • Surface Plasmon Resonance
  • Vaccination / methods*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • Influenza Vaccines
  • Vaccines, DNA
  • Vaccines, Inactivated

Associated data

  • ClinicalTrials.gov/NCT01086657