Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response.
Long-term immunity to Leishmania may require the continued presence of parasites, but previous attempts to create attenuated parasites that persist without causing disease have had limited success. Since Leishmania major mutants that lack lipophosphoglycan and other secreted phosphoglycans, termed lpg2-, persist indefinitely in infected mice without inducing any disease, we tested their ability to provide protection to virulent L. major challenge. In response to leishmanial Ag stimulation, cells from lpg2--infected mice produced minimal levels of IL-4 and IL-10, as well as very low levels of IFN-gamma. Nevertheless, when BALB/c mice infected with lpg2- parasites were challenged with virulent L. major they were protected from disease. Thus, these findings report on attenuated parasites that may be used to induce long-term protection against leishmaniasis and indicate that the immunity induced can be maintained in the absence of a strong Th1 response.
Uzonna
Jude E
JE
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Späth
Gerald F
GF
Beverley
Stephen M
SM
Scott
Phillip
P
D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D006028:Glycosphingolipids / Q000172:deficiency* / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018320:Leishmania major / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D015800:Protozoan Proteins / Q000235:genetics; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics / Q000276:immunology
D006028:Glycosphingolipids; C095909:LPG2 protein, Leishmania; D008565:Membrane Proteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated; C008290:lipophosphonoglycan; D016753:Interleukin-10; D015847:Interleukin-4