title: Effective adjuvants for the induction of antigen-specific delayed-type hypersensitivity.
abstract: Vaccines utilizing poorly immunogenic subunit antigens are dependent upon adjuvants to drive the appropriate T cell responses. In an effort to determine the ability of several adjuvants to promote cell-mediated immunity (CMI), we assessed delayed-type hypersensitivity (DTH) in mice inoculated with heat-killed Listeria monocytogenes (HKLM) vaccines. The vaccines were formulated as oil-in-water emulsions containing one or more of the following bacterial-derived immunostimulators: MPL immunostimulant, a monophosphoryl lipid A preparation, synthetic trehalose dicorynomycolate (TDCM) and Mycobacterium phlei cell wall skeleton (CWS). Oil-in-water emulsions containing HKLM without adjuvants did not induce DTH responsiveness in mice. The incorporation of TDCM, or MPL plus TDCM and/or CWS to the formulation enabled the HKLM vaccine to stimulate CMI characterized by DTH responsiveness. Following antigen challenge the resulting increases in footpad thickness ranged from 15-20% and were comparable to the DTH driven by complete Freund's adjuvant. Adjuvants composed of MPL/TDCM and MPL/TDCM/CWS induced responses equivalent to those measured in mice immunized with viable L. monocytogenes, and the responses remained at these levels for at least 2 months. Furthermore, in vivo depletion of CD4+ T cells, but not CD8+ T cells, abrogated the induction and expression of DTH, indicating that the response is mediated by CD4+ T cells.
authors.affiliation: Ribi ImmunoChem Research, Inc., Hamilton, MT 59840, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Baldridge
authors.forename: J R
authors.initials: JR
authors.lastname: Ward
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008089:Listeria monocytogenes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D000939:Epitopes; D015164:Vaccines, Inactivated