A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection.
Buruli ulcer (BU) disease, a neglected necrotizing tropical skin infection caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. Infections mostly occur in remote, rural areas of Central and West Africa, but also in Australia, Japan and Papu...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-02-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0012710 |
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| author | Justice Kofi Boakye-Appiah Andy C Tran Matthew J Paul Peter Hart Richard O Phillips Thomas S Harrison Mark Wansbrough-Jones Rajko Reljic |
| author_facet | Justice Kofi Boakye-Appiah Andy C Tran Matthew J Paul Peter Hart Richard O Phillips Thomas S Harrison Mark Wansbrough-Jones Rajko Reljic |
| author_sort | Justice Kofi Boakye-Appiah |
| collection | DOAJ |
| description | Buruli ulcer (BU) disease, a neglected necrotizing tropical skin infection caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. Infections mostly occur in remote, rural areas of Central and West Africa, but also in Australia, Japan and Papua New Guinea. There is currently no vaccine against Buruli ulcer disease and all previous attempts using closely related bacteria and subunit proteins have been partially successful only. Here, we tested in mice a composite subunit formulation incorporating the Mycobacterium ulcerans toxin mycolactone as the immunomodulator, and the antigens Ag85A and Polyketide Synthase Enzyme Ketoreductase A (KRA), formulated with Quil-A adjuvant ('Burulivac'). Burulivac induced Ag85A and KRA antigen-specific antibodies, T cells and a mixed pro- and anti-inflammatory cytokine responses, which conferred absolute protection against Buruli ulcer disease in the mouse footpad model over a 14-week period of observation. This was superior to both live attenuated mycobacterial vaccines, that is, BCG and an avirulent M. ulcerans strain that lacks the mycolactone toxin (MuΔ). Interleukin 10 was found to be strongly associated with protection. We suggest that Burulivac is a promising vaccine candidate against Buruli ulcer disease that warrants further exploration. |
| format | Article |
| id | doaj-art-e6446a80c65a48a3a8d45f72196d7a6f |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-e6446a80c65a48a3a8d45f72196d7a6f2025-08-20T02:15:12ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352025-02-01192e001271010.1371/journal.pntd.0012710A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection.Justice Kofi Boakye-AppiahAndy C TranMatthew J PaulPeter HartRichard O PhillipsThomas S HarrisonMark Wansbrough-JonesRajko ReljicBuruli ulcer (BU) disease, a neglected necrotizing tropical skin infection caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy. Infections mostly occur in remote, rural areas of Central and West Africa, but also in Australia, Japan and Papua New Guinea. There is currently no vaccine against Buruli ulcer disease and all previous attempts using closely related bacteria and subunit proteins have been partially successful only. Here, we tested in mice a composite subunit formulation incorporating the Mycobacterium ulcerans toxin mycolactone as the immunomodulator, and the antigens Ag85A and Polyketide Synthase Enzyme Ketoreductase A (KRA), formulated with Quil-A adjuvant ('Burulivac'). Burulivac induced Ag85A and KRA antigen-specific antibodies, T cells and a mixed pro- and anti-inflammatory cytokine responses, which conferred absolute protection against Buruli ulcer disease in the mouse footpad model over a 14-week period of observation. This was superior to both live attenuated mycobacterial vaccines, that is, BCG and an avirulent M. ulcerans strain that lacks the mycolactone toxin (MuΔ). Interleukin 10 was found to be strongly associated with protection. We suggest that Burulivac is a promising vaccine candidate against Buruli ulcer disease that warrants further exploration.https://doi.org/10.1371/journal.pntd.0012710 |
| spellingShingle | Justice Kofi Boakye-Appiah Andy C Tran Matthew J Paul Peter Hart Richard O Phillips Thomas S Harrison Mark Wansbrough-Jones Rajko Reljic A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection. PLoS Neglected Tropical Diseases |
| title | A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection. |
| title_full | A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection. |
| title_fullStr | A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection. |
| title_full_unstemmed | A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection. |
| title_short | A composite subunit vaccine confers full protection against Buruli ulcer disease in the mouse footpad model of Mycobacterium ulcerans infection. |
| title_sort | composite subunit vaccine confers full protection against buruli ulcer disease in the mouse footpad model of mycobacterium ulcerans infection |
| url | https://doi.org/10.1371/journal.pntd.0012710 |
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