title: Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults.
abstract: Recombinant subunit protein vaccines generally elicit good humoral immune responses, weak helper T cell responses and no cytotoxic T cell responses. Certain adjuvants are known to enhance humoral and cellular immune responses. This study evaluated the humoral, CD4+ T helper and CTL responses induced by the recombinant SL* protein adjuvanted with AS02A in comparison with non-adjuvanted SL* in PBS in two groups of 15 healthy adult volunteers. The AS02A adjuvant contains monophosphoryl lipid A (MPL), QS21 and an oil in water emulsion. The adjuvanted vaccine induced fast and vigorous humoral and helper T cell responses of the Th1 type. Using a pool of overlapping 20mer peptides a cytotoxic response was detected in 6 out of 14 HLA-A2-positive (+) and HLA-A2-negative (-) recipients of the adjuvanted vaccine. All HLA-A2-positive subjects in the adjuvanted group and up to 30% of the subjects in the SL* PBS group displayed a CTL response against selected HLA-A2-restricted CD8+ T cell epitopes. The non-adjuvanted vaccine induced a very weak antibody response and no helper T cell responses. Local and general reactions were more frequently reported by AS02A recipients than in the non-adjuvanted group but the safety profile was considered acceptable. AS02A can be considered as a useful adjuvant that strongly enhances the cellular and humoral responses of subunit protein vaccines.
authors.affiliation: GlaxoSmithKline Biologicals, 89 Rue de 1'institut, B-1330 Rixensart, Belgium. pierre.vandepapeliere@gskbio.com
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Nathalie
authors.initials: N
authors.lastname: Garçon
authors.forename: Martine
authors.initials: M
authors.lastname: Wettendorff
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D000328:Adult; D000595:Amino Acid Sequence; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D004338:Drug Combinations; D006510:Hepatitis B Antibodies / Q000032:analysis / Q000096:biosynthesis; D017325:Hepatitis B Vaccines / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D010835:Phytohemagglutinins; D012503:Saponins / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D016207:Cytokines; D004338:Drug Combinations; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D015848:Interleukin-5; D008050:Lipid A; D010835:Phytohemagglutinins; D012503:Saponins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma