Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults

Vaccine. 2005 Apr 8;23(20):2591-601. doi: 10.1016/j.vaccine.2004.11.034.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / pharmacology*
  • Adult
  • Amino Acid Sequence
  • Antibody Formation / drug effects*
  • Antibody Formation / immunology*
  • Cell Proliferation
  • Cell Separation
  • Cytokines / biosynthesis
  • Drug Combinations
  • Hepatitis B Antibodies / analysis
  • Hepatitis B Antibodies / biosynthesis
  • Hepatitis B Vaccines / adverse effects
  • Hepatitis B Vaccines / immunology*
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / genetics
  • Lipid A / analogs & derivatives*
  • Lipid A / pharmacology*
  • Molecular Sequence Data
  • Neutrophils / immunology
  • Phytohemagglutinins
  • Saponins / pharmacology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Synthetic / immunology

Substances

  • ASO2A adjuvant
  • Adjuvants, Immunologic
  • Cytokines
  • Drug Combinations
  • Hepatitis B Antibodies
  • Hepatitis B Vaccines
  • Interleukin-5
  • Lipid A
  • Phytohemagglutinins
  • Saponins
  • Vaccines, Synthetic
  • Interferon-gamma