title: H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses.
abstract: OBJECTIVE
  Adjuvantation of an H5N1 split-virion influenza vaccine with AS03(A) substantially reduces the antigen dose required to produce a putatively protective humoral response and promotes cross-clade neutralizing responses. We determined the effect of adjuvantation on antibody persistence and B- and T-cell-mediated immune responses.
  
  
  METHODS
  Two vaccinations with a split-virion A/Vietnam/1194/2004 (H5N1, clade 1) vaccine containing 3.75-30 μg hemagglutinin and formulated with or without adjuvant were administered to groups of 50 volunteers aged 18-60 years.
  
  
  RESULTS
  Adjuvantation of the vaccine led to better persistence of neutralizing and hemagglutination-inhibiting antibodies and higher frequencies of antigen-specific memory B cells. Cross-reactive and polyfunctional H5N1-specific CD4 T cells were detected at baseline and were amplified by vaccination. Expansion of CD4 T cells was enhanced by adjuvantation.
  
  
  CONCLUSIONS
  Formulation of the H5N1 vaccine with AS03(A) enhances antibody persistence and induces stronger T- and B-cell responses. The cross-clade T-cell immunity indicates that the adjuvanted vaccine primes individuals to respond to either infection and/or subsequent vaccination with strains drifted from the primary vaccine strain.
authors.affiliation: GlaxoSmithKline Biologicals, Rixensart, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Robbert
authors.initials: R
authors.lastname: van der Most
authors.forename: Isabel
authors.initials: I
authors.lastname: Leroux-Roels
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clement
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hanon
authors.forename: Geert G
authors.initials: GG
authors.lastname: Leroux-Roels
authors.forename: Marcelle
authors.initials: M
authors.lastname: Van Mechelen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D004196:Disease Outbreaks / Q000517:prevention & control*; D005260:Female; D006388:Hemagglutinins / Q000097:blood / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007156:Immunologic Memory; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000276:immunology; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006388:Hemagglutinins; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated