title: 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.
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.
authors: Division of Viral Products,National Institute of Allergyand Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. surender.khurana@fda.hhs.gov
authors: Surender
authors: S
authors: Khurana
authors: Jian
authors: J
authors: Wu
authors: Milena
authors: M
authors: Dimitrova
authors: Lisa R
authors: LR
authors: King
authors: Jody
authors: J
authors: Manischewitz
authors: Barney S
authors: BS
authors: Graham
authors: Julie E
authors: JE
authors: Ledgerwood
authors: Hana
authors: H
authors: Golding
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D000915:Antibody Affinity; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020349:Surface Plasmon Resonance; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated
keywords: H5N1; Phage display; SPR; affinity; antibody; epitope; hemagglutinin; immune response; influenza; vaccine; virus
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