title: Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.
abstract: Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471.
authors.affiliation: Department of Microbiology and Infectious Diseases, SA Pathology, Flinders Medical Centre, and Flinders University, South Australia 5042, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Gordon
authors.affiliation: Australian Respiratory and Sleep Medicine Institute, Adelaide, South Australia 5042, Australia.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Sajkov
authors.affiliation: Department of Endocrinology, Flinders University, 5042, Australia; Vaxine Pty Ltd, Flinders Medical Centre, Adelaide 5042, Australia.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Honda-Okubo
authors.affiliation: Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK; World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Wilks
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza (VIDRL), Peter Doherty Institute for Infection & Immunity, 792 Elizabeth Street, Melbourne 3000, Australia.
authors.forename: Malet
authors.initials: M
authors.lastname: Aban
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza (VIDRL), Peter Doherty Institute for Infection & Immunity, 792 Elizabeth Street, Melbourne 3000, Australia; Department of Microbiology & Immunology, University of Melbourne, Victoria 3000, Australia.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Barr
authors.affiliation: Australian Respiratory and Sleep Medicine Institute, Adelaide, South Australia 5042, Australia; Department of Endocrinology, Flinders University, 5042, Australia; Vaxine Pty Ltd, Flinders Medical Centre, Adelaide 5042, Australia. Electronic address: nikolai.petrovsky@flinders.edu.au.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D007444:Inulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D015164:Vaccines, Inactivated / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; C576871:delta inulin; D007444:Inulin
keywords: Adjuvant; Advax; Delta inulin; Immunogenicity; Influenza; Safety; Vaccine