1. Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: a randomized controlled clinical trial.
- Author
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Langley JM, Frenette L, Jeanfreau R, Halperin SA, Kyle M, Chu L, McNeil S, Dramé M, Moris P, Fries L, and Vaughn DW
- Subjects
- Adjuvants, Immunologic administration & dosage, Adolescent, Adult, Aged, Aged, 80 and over, Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, Drug Combinations, Female, Hemagglutination Inhibition Tests, Humans, Indonesia, Influenza, Human virology, Leukocytes, Mononuclear immunology, Male, Middle Aged, Neutralization Tests, Placebos administration & dosage, Polysorbates administration & dosage, Single-Blind Method, Squalene administration & dosage, Turkey, Young Adult, alpha-Tocopherol administration & dosage, Immunization, Secondary methods, Influenza A Virus, H5N1 Subtype immunology, Influenza Vaccines administration & dosage, Influenza Vaccines immunology, Influenza, Human prevention & control
- 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., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2015
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