Leishmania infantum sterol 24-c-methyltransferase formulated with MPL-SE induces cross-protection against L. major infection.
The enzyme sterol 24-c-methyltranferase (SMT) is required for the biosynthesis of ergosterol, the major membrane sterol in Leishmania parasites. SMT and ergosterol are not found in mammals, so this protein may be an attractive target for anti-leishmanial vaccines and drugs. We have previously demonstrated that SMT from L. infantum, which causes visceral leishmaniasis, is a protective antigen against this parasite. Because this protein is highly conserved among Leishmania species, we evaluated the potential of SMT to cross-protect against a different form of leishmaniasis. Here, we show that immunization with L. infantum SMT, formulated with monophosphoryl lipid A in stable emulsion (MPL-SE), protects mice from cutaneous leishmaniasis caused by L. major. In BALB/c mice the vaccine preparation induced antigen-specific multi-functional CD4(+) T cells capable of producing IFN-gamma, IL-2, and/or TNF-alpha upon antigen re-exposure, and MPL-SE was indispensable to direct immune responses to SMT towards Th1. Mice immunized with the SMT/MPL-SE vaccine developed significantly smaller lesions following ear challenge with L. major. These results suggest that SMT is a promising vaccine antigen for multiple forms of leishmaniasis.
Goto
Yasuyuki
Y
Infectious Disease Research Institute, 1124 Columbia St, Suite 400, Seattle, WA 98104, USA. ygoto@idri.org
Bhatia
Ajay
A
Raman
Vanitha S
VS
Vidal
Silvia E Z
SE
Bertholet
Sylvie
S
Coler
Rhea N
RN
Howard
Randall F
RF
Reed
Steven G
SG
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D006224:Cricetinae; D003429:Cross Reactions / Q000276:immunology; D004655:Emulsions; D005260:Female; D018314:Leishmania infantum / Q000201:enzymology* / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control*; D008780:Methyltransferases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000953:Antigens, Protozoan; D004655:Emulsions; D008780:Methyltransferases; C022670:delta 24-sterol methyltransferase