title: Galactose oxidation as a potent vaccine adjuvant strategy. Efficacy in murine models and in protection against a bovine parasitic infection.
abstract: Potent immunological adjuvants are urgently required to complement subunit protein and peptide vaccines in prophylactic and therapeutic vaccination. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T-helper cells, were tested as a target for the enhancement or immune responses to vaccine antigens. Enzymic oxidation of cell surface galactose by the novel adjuvant NAGO, to increase amine-reactive carbonyl groups on lymphocytes and antigen-presenting cells, provided a potent noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice. In pilot protection studies with a glutathione-S-transferase vaccine against bovine Fasciola hepatica, a formulation containing NAGO as sole adjuvant agent proved very effective in inducing protection. In terms of protection in individual animals, NAGO alone was better than Quil A emulsified in squalene Montanide (five of eight animals were protected better than 80% by NAGO; four of eight animals were protected better than 93% by NAGO; two of eight animals were protected better than 80% by QA/SM). QA/SM (69% mean protection) was, however, more consistent overall than NAGO (65% mean protection). NAGO proved more effective in murine models when combined with muramyl dipeptide, but this combination has yet to be tested in protection studies.
authors.affiliation: Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Rhodes
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.forename: C A
authors.initials: CA
authors.lastname: Morrison
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D002417:Cattle; D003602:Cytotoxicity, Immunologic; D005210:Fasciola hepatica / Q000276:immunology; D005211:Fascioliasis / Q000517:prevention & control*; D005260:Female; D005692:Galactose Oxidase / Q000276:immunology*; D005982:Glutathione Transferase / Q000276:immunology; D006968:Hypersensitivity, Delayed; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014612:Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D000914:Antibodies, Viral; D001428:Bacterial Vaccines; D016052:Protozoan Vaccines; D014612:Vaccines; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005692:Galactose Oxidase; D005982:Glutathione Transferase; D009439:Neuraminidase