TABLE 1.
Summary of putative M. ulcerans vaccines tested in a murine model of BU infectiona
| Vaccine type | Description of components | M. ulcerans challenge dose (strain)b | Challenge model | Efficacy compared to BCG | Reference(s) |
|---|---|---|---|---|---|
| DNA based | pCDNA3 vector encoding Hsp65 | 104 AFB (1615 ATCC 35840) | Tail | Less protective | 52 |
| DNA based | V1Jns.tPA vector encoding Ag85A | 3 × 104 AFB (5150) or 105 AFB (04-855) | Footpad | Less protective | 32, 33 |
| DNA based | Primary vaccination with V1Jns.tPA plasmid encoding mycolactone polyketide domains and boosted with recombinant domain proteins emulsified in Gerbu adjuvant | 105 AFB (1615) | Footpad | Less protective | 49 |
| Viral | Vesicular stomatitis virus replicon particles expressing M. ulcerans codon optimized antigens MUL_2232 and MUL_3720 | 30 μl of 2.8 × 105 CFU/ml stock (8.4 × 103 CFU/dose) (S1013) | Footpad | Less protective | 108 |
| Subunit | MUL2232 and MUL3720 adjuvanted with GLA-SE (EM408) | 1.5 × 106 or 1.5 × 105 CFU (S1013) | Footpad | Less protective | 34 |
| Live cell | M. ulcerans | 106.3 or 104.3 viable bacteria | Footpad | Less protective | 109 |
| Live cell | M. marinum | 105 bacteria (1615) | Footpad | More protectivec | 35 |
| Live cell recombinant | M. marinum expressing Ag85A (on vector) | 105 bacteria (1615) | Footpad | More protectivec | 35 |
| Live cell recombinant | M. bovis BCG expressing Ag85A (on vector pMV261) | 105 bacteria (1615) | Footpad | More protective | 36 |
| Live cell recombinant | M. bovis BCG expressing Ag85B-EsxH fusion protein Ag85A (on vector pMV261) | 105 bacteria (1615) | Footpad | More protective | 37 |
| Inactivated whole cell | Mycolactone-negative M. ulcerans (strain 5114) | 4 log10 or 3 log10 CFU (98-912) | Footpad | Less protective | 25 |
| Inactivated whole cell | Mycolactone-deficient attenuated M. ulcerans (strain ATCC 19423) | 106 bacteria (TMC1615) | Footpad | Not compared | 54 |
| Inactivated whole cell | Formalin-treated M. ulcerans (strain TMC1615) | 106 bacteria (TMC1615) | Footpad | Not compared | 54 |
| Inactivated whole cell | Dewaxed M. ulcerans (strain TMC1615) | 106 bacteria (TMC1615) | Footpad | Not compared | 54 |
| Phage | Mycobacteriophage D29 (therapeutic vaccine) | 5.5 log10 AFB (1615) | Footpad | Not comparable | 53 |
a
No test of whether the bacterial culture used for challenge was assessed for mycolactone production before infection was mentioned with any of the vaccines.
b
AFB, acid-fast bacilli.
c
Vaccine was more protective than the BCG vaccine; however, all mice eventually developed footpad swelling.