title: Induction of protective and mucosal immunity against diphtheria by a immune stimulating complex (ISCOMS) based vaccine.
abstract: There is increasing concern over the efficacy of existing vaccines for diphtheria and there is interest in the development of a mucosally active formulation which might improve local protection. Lipophilic immune stimulating complexes (ISCOMS) containing Quil A are active by both parenteral and mucosal routes and here we have established methods for incorporating palmitified diphtheria toxoid (DT) into ISCOMS. The resulting formulation was immunogenic by the subcutaneous, oral and intranasal routes, with very low doses of DT inducing systemic humoral immune responses, as well as cell mediated immunity including both gammaIFN and IL5 production. Intranasal immunisation with DT in ISCOMS also stimulated significant local antibody production in tracheal washes, as well as cellular immunity in draining lymphoid tissues and serum neutralising antibodies. Finally, subcutaneous immunisation of guinea pigs with DT in ISCOMS primed protective immunity against challenge with diphtheria holotoxin more efficiently than the equivalent doses of DT in the conventional alum vaccine. ISCOMS based vaccines may provide a novel strategy for mucosal and systemic immunisation against diphtheria.
authors.affiliation: Division of Immunology, Infection and Inflammation, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow, Scotland G12 8TA, United Kingdom.
authors.forename: Antonio
authors.initials: A
authors.lastname: Aguila
authors.forename: Anne M
authors.initials: AM
authors.lastname: Donachie
authors.forename: Marisa
authors.initials: M
authors.lastname: Peyre
authors.forename: Charles P
authors.initials: CP
authors.lastname: McSharry
authors.forename: Dorothea
authors.initials: D
authors.lastname: Sesardic
authors.forename: Allan McI
authors.initials: AM
authors.lastname: Mowat
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004168:Diphtheria Toxoid / Q000008:administration & dosage*; D005260:Female; D006168:Guinea Pigs; D016882:ISCOMs / Q000008:administration & dosage*; D018928:Immunity, Mucosal; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D016882:ISCOMs; D007074:Immunoglobulin G