title: Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: a randomized controlled clinical trial.
abstract: BACKGROUND
  Highly pathogenic avian influenza A/H5N1 viruses continue to circulate in birds and infect humans causing serious illness and death.
  
  
  METHODS
  In this randomized, observer-blinded study, adults ≥18 years of age (n=841) received 3.75 or 7.5 μg hemagglutinin antigen (HA) of an AS03-adjuvanted (AS03A or AS03B) A/Indonesia/5/2005 H5N1 (subclade 2.1) vaccine (priming), followed by the same HA dose of AS03-adjuvanted A/turkey/Turkey/1/05 H5N1 (clade 2.2) influenza vaccine as a booster 6 or 18 months after priming; an unprimed group received placebo at Day 0, and 3.75 μg HA of AS03A-adjuvanted booster vaccine at 6 and 18 months. Antibody responses were assessed by hemagglutination-inhibition assay (HI). Microneutralization (MN) antibody and cellular immunoassays were assessed in a subset of participants.
  
  
  RESULTS
  Geometric mean titers (GMTs) and seroconversion rates (SCRs) were higher in primed vs. unprimed subjects against the booster strain 10 days following booster vaccination at month 6 and month 18. After the booster at 18 months, the lower limit of the 97.5% confidence interval for the difference in SCR and GMT ratios between primed and unprimed subjects was >15% and >2.0, respectively, fulfilling the primary endpoint criteria for superiority against the booster strain. MN and cellular immune responses corresponded with the immunogenicity seen in HI measures.
  
  
  CONCLUSIONS
  Adults primed with a dose-sparing oil-in-water adjuvanted H5N1 subclade vaccine had rapid and durable antibody responses to a heterologous subclade boosting vaccine given 6 or 18 months later.
authors.affiliation: Canadian Center for Vaccinology, 5850 University Avenue, Dalhousie University, IWK Health Centre and Capital Health District, Halifax, B3K 6R8 Canada. Electronic address: jmlangle@dal.ca.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Langley
authors.affiliation: QT Research, 2185 King Ouest Suite 101, Sherbrooke, J1J Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Frenette
authors.affiliation: Benchmark Research, 3800 Houma Blvd., Suite 205, Metairie, LA 70006, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Jeanfreau
authors.affiliation: Canadian Center for Vaccinology, 5850 University Avenue, Dalhousie University, IWK Health Centre and Capital Health District, Halifax, B3K 6R8 Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Halperin
authors.affiliation: Pfizer Inc, 235 E 42nd St., New York, NY, 10017, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kyle
authors.affiliation: Benchmark Research, 1015 E 32nd Suite 309, Austin, TX 78705-2701, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Chu
authors.affiliation: Canadian Center for Vaccinology, 5850 University Avenue, Dalhousie University, IWK Health Centre and Capital Health District, Halifax, B3K 6R8 Canada.
authors.forename: Shelly
authors.initials: S
authors.lastname: McNeil
authors.affiliation: GlaxoSmithKline Vaccines, 2301 Renaissance Blvd, King of Prussia, PA 19406-2772, USA.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut, 89 BE-1330 Rixensart, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Fries
authors.affiliation: GlaxoSmithKline Vaccines, Rue de l'Institut, 89 BE-1330 Rixensart, Belgium.
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004338:Drug Combinations; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007214:Indonesia; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010919:Placebos / Q000008:administration & dosage; D011136:Polysorbates / Q000008:administration & dosage; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage; D014421:Turkey; D055815:Young Adult; D024502:alpha-Tocopherol / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D010919:Placebos; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
keywords: Heterologous booster; Immunogenicity; Influenza A/H5N1 vaccine