Buruli ulcer

Figures & data

Table 1. Summary table of possible vaccine approaches. Listed are the vaccine targets (toxin, bacteria or specific protein) and type, whether the vaccines are specific for M. ulcerans or cross-react with other mycobacteria. Results from experimental models and published immune responses in humans are listed, as well as whether the vaccine has been tested in clinical trials for protection against BU disease

Vaccine target	Antigen(s)	Type of vaccine	Breadth and specificity of response	Protection in experimental models	Immune response in humans	Clinical trial results	References
Toxin
	1) ML toxin	Inactivated toxin and/or conjugated to a protein-carrier	Narrow, M. ulcerans-specific	Active toxin causes disease. Weak induction of immune responses	Not detected	Not tested	^25
	2) Enzymes that synthesize ML	DNA vaccine or protein vaccine	Narrow, M. ulcerans-specific	Work in progress	Humoral response shown. Cellular response not tested	Not tested	^28
Whole bacteria
	1) BCG	Live, attenuated bacteria	Broad, cross-reactive	Transient protection in mice	Humoral and cellular	Transient protection	^40 ^- ^43 ^, ^48
	2) BCG + boost with protein or viral vector expressing immunodominant antigen	Live, attenuated bacteria + viral vector or protein vaccine	Broad, cross-reactive	Not tested for M. ulcerans ^(a)	Not tested for M. ulcerans ^(a)	Not tested for M. ulcerans ^(a)	^37 ^, ^38
	3) Recombinant BCG expressing M. ulcerans antigens	Live, attenuated bacteria	Broad, cross-reactive	Not tested	Not tested	Not tested
	4) ML-deficient M. ulcerans	Live, attenuated bacteria	Broad, cross-reactive	Work in progress	Not tested	Not tested
Single antigen
	1) Mycobacterial proteins	DNA vaccine or protein vaccine	Narrow, cross-reactive	Transient protection in mice	Humoral and cellular	Not tested	^27 ^, ^51 ^, ^52
	2) M. ulcerans specific proteins	DNA vaccine or protein vaccine	Narrow, M. ulcerans- specific	Not tested	Humoral. Cellular response not tested	Not tested	^26 ^, ^28

(a) Results from TB vaccine research are promising and indicate this strategy may show efficacy against BU.

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BCG vaccination against Mycobacterium ulcerans infection (Buruli ulcer). First results of a trial in Uganda. Lancet 1969; 1:111 - 5; PMID: 4178240

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Portaels F, Aguiar J, Debacker M, Guedenon A, Steunou C, Zinsou C, et al. Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease. Infect Immun 2004; 72:62 - 5; http://dx.doi.org/10.1128/IAI.72.1.62-65.2004; PMID: 14688081

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Tanghe A, Adnet PY, Gartner T, Huygen K. A booster vaccination with Mycobacterium bovis BCG does not increase the protective effect of the vaccine against experimental Mycobacterium ulcerans infection in mice. Infect Immun 2007; 75:2642 - 4; http://dx.doi.org/10.1128/IAI.01622-06; PMID: 17325046

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McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, et al. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 2004; 10:1240 - 4; http://dx.doi.org/10.1038/nm1128; PMID: 15502839

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Diaz D, Dobeli H, Yeboah-Manu D, Mensah-Quainoo E, Friedlein A, Soder N, et al. Use of the immunodominant 18-kiloDalton small heat shock protein as a serological marker for exposure to Mycobacterium ulcerans.. Clin Vaccine Immunol 2006; 13:1314 - 21; http://dx.doi.org/10.1128/CVI.00254-06; PMID: 17021247

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Tanghe A, Dangy JP, Pluschke G, Huygen K. Improved protective efficacy of a species-specific DNA vaccine encoding mycolyl-transferase Ag85A from Mycobacterium ulcerans by homologous protein boosting. PLoS Negl Trop Dis 2008; 2:e199; http://dx.doi.org/10.1371/journal.pntd.0000199; PMID: 18350112

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Coutanceau E, Legras P, Marsollier L, Reysset G, Cole ST, Demangel C. Immunogenicity of Mycobacterium ulcerans Hsp65 and protective efficacy of a Mycobacterium leprae Hsp65-based DNA vaccine against Buruli ulcer. Microbes Infect 2006; 8:2075 - 81; http://dx.doi.org/10.1016/j.micinf.2006.03.009; PMID: 16781179

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Tanghe A, Content J, Van Vooren JP, Portaels F, Huygen K. Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer. Infect Immun 2001; 69:5403 - 11; http://dx.doi.org/10.1128/IAI.69.9.5403-5411.2001; PMID: 11500410

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