Induction of protective and mucosal immunity against diphtheria by a immune stimulating complex (ISCOMS) based vaccine

Aguila, A., Donachie, A. M., Peyre, M., McSharry, C. P., Sesardic, D. and Mowat, A. M. (2006) Induction of protective and mucosal immunity against diphtheria by a immune stimulating complex (ISCOMS) based vaccine. Vaccine, 24, pp. 5201-5210. (doi:10.1016/j.vaccine.2006.03.081) (PMID:16650917)

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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 γIFN 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan and Donachie, Ms Anne Marie and McSharry, Dr Charles
Authors: Aguila, A., Donachie, A. M., Peyre, M., McSharry, C. P., Sesardic, D., and Mowat, A. M.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Vaccine
Publisher:Elsevier
ISSN:0264-410X
ISSN (Online):1873-2518
Published Online:17 April 2006

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
284131Development of mucosally active ISCOMS based diptheria toxoid vaccineAllan MowatWellcome Trust (WELLCOME)062062/Z/00/ZInfection Immunity and Inflammation Medicine