There is no effective
vaccine against
Buruli ulcer. In experimental footpad
infection of C57BL/6 mice with M. ulcerans, a prime-boost vaccination protocol using plasmid
DNA encoding mycolyltransferase Ag85A of M. ulcerans and a homologous
protein boost has shown significant, albeit transient protection, comparable to the one induced by M. bovis BCG. The
mycolactone toxin is an obvious candidate for a
vaccine, but by virtue of its chemical structure, this toxin is not immunogenic in itself. However,
antibodies against some of the
polyketide synthase domains involved in
mycolactone synthesis, were found in
Buruli ulcer patients and healthy controls from the same endemic region, suggesting that these domains are indeed immunogenic. Here we have analyzed the
vaccine potential of nine
polyketide synthase domains using
a DNA prime/
protein boost strategy. C57BL/6 mice were vaccinated against the following domains:
acyl carrier protein 1, 2, and 3,
acyltransferase (
acetate) 1 and 2,
acyltransferase (
propionate), enoylreductase, ketoreductase A, and ketosynthase load module. As positive controls, mice were vaccinated with
DNA encoding Ag85A or with M. bovis BCG. Strongest
antigen specific
antibodies could be detected in response to
acyltransferase (
propionate) and enoylreductase.
Antigen-specific Th1 type
cytokine responses (IL-2 or IFN-γ) were induced by vaccination against all
antigens, and were strongest against
acyltransferase (
propionate). Finally, vaccination against
acyltransferase (
propionate) and enoylreductase conferred some protection against challenge with virulent M. ulcerans 1615. However, protection was weaker than the one conferred by vaccination with Ag85A or M. bovis BCG. Combinations of these
polyketide synthase domains with the
vaccine targeting Ag85A, of which the latter is involved in the integrity of the cell wall of the pathogen, and/or with live attenuated M. bovis BCG or
mycolactone negative M. ulcerans may eventually lead to the development of an efficacious BU
vaccine.