Protective immunization against visceral leishmaniasis using Leishmania sterol 24-c-methyltransferase formulated in adjuvant.
We present here the identification and characterization of Leishmania sterol 24-c-methyltransferase (SMT), as well as data on protection of mice immunized with this Ag formulated in MPL-SE. Serological evaluation revealed that SMT is recognized by VL patients. C57BL/6 mice immunized with this vaccine candidate plus MPL-SE showed Ag-specific Th1 immune responses characterized by robust production of IFN-gamma upon specific Ag re-exposure in vitro. Upon challenge with L. infantum, mice immunized with SMT plus MPL-SE showed significant lower parasite burdens in both spleens and livers compared with non-immunized mice or mice injected with adjuvant alone. The results indicate that SMT/MPL-SE can be an effective vaccine candidate for use against VL.
Goto
Yasuyuki
Y
Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104, USA.
Bogatzki
Lisa Y
LY
Bertholet
Sylvie
S
Coler
Rhea N
RN
Reed
Steven G
SG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018314:Leishmania infantum / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control*; D008780:Methyltransferases / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology