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Vaccination with the surface proteins MUL_2232 and MUL_3720 of Mycobacterium ulcerans induces antibodies but fails to provide protection against Buruli ulcer

Bolz, Miriam and Bénard, Angèle and Dreyer, Anita M. and Kerber, Sarah and Vettiger, Andrea and Oehlmann, Wulf and Singh, Mahavir and Duthie, Malcolm S. and Pluschke, Gerd. (2016) Vaccination with the surface proteins MUL_2232 and MUL_3720 of Mycobacterium ulcerans induces antibodies but fails to provide protection against Buruli ulcer. PLoS neglected tropical diseases, 10 (2). e0004431.

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Abstract

Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a chronic ulcerative neglected tropical disease of the skin and subcutaneous tissue that is most prevalent in West African countries. M. ulcerans produces a cytotoxic macrolide exotoxin called mycolactone, which causes extensive necrosis of infected subcutaneous tissue and the development of characteristic ulcerative lesions with undermined edges. While cellular immune responses are expected to play a key role against early intracellular stages of M. ulcerans in macrophages, antibody mediated protection might be of major relevance against advanced stages, where bacilli are predominantly found as extracellular clusters.; To assess whether vaccine induced antibodies against surface antigens of M. ulcerans can protect against Buruli ulcer we formulated two surface vaccine candidate antigens, MUL_2232 and MUL_3720, as recombinant proteins with the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion. The candidate vaccines elicited strong antibody responses without a strong bias towards a TH1 type cellular response, as indicated by the IgG2a to IgG1 ratio. Despite the cross-reactivity of the induced antibodies with the native antigens, no significant protection was observed against progression of an experimental M. ulcerans infection in a mouse footpad challenge model.; Even though vaccine-induced antibodies have the potential to opsonise the extracellular bacilli they do not have a protective effect since infiltrating phagocytes might be killed by mycolactone before reaching the bacteria, as indicated by lack of viable infiltrates in the necrotic infection foci.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Molecular Immunology (Pluschke)
UniBasel Contributors:Bolz, Miriam and Dreyer, Anita and Bénard, Angèle and Vettiger, Andrea and Pluschke, Gerd
Item Type:Article, refereed
Publisher:Public Library of Science
ISSN:1935-2727
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:25 Aug 2016 10:24
Deposited On:28 Apr 2016 08:10

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