Protective immune response against cutaneous leishmaniasis by prime/booster immunization regimens with vaccinia virus recombinants expressing Leishmania infantum p36/LACK and IL-12 in combination with purified p36.
In susceptible mice Leishmania infection triggers a CD4(+) Th2 response that has been correlated with evasion of the host immune system. To develop approaches that might trigger a Th1 response leading to protection against Leishmania we generated vaccinia virus recombinants (VVr) expressing the relevant p36/LACK protein of Leishmania infantum (VVp36) or co-expressing p36/LACK and interleukin-12 (VVp36IL12). Susceptible BALB/c mice were immunized with the VVr in various prime/booster protocols that included purified p36/LACK protein, followed 3 weeks later by a challenge with live L. major promastigotes. The course of the infection was monitored by measuring lesion development, parasite load and immunological parameters (IFN-gamma and IL-10 secretion by in vitro-stimulated lymphocytes, and specific IgG isotypes), before and after challenge. We found protocols of prime/booster immunization (VVp36/VVp36; VVp36IL12/p36; p36/VVp36IL12) that elicited different levels of protection in infected animals. The protocol of priming with purified p36 followed by a booster with VVp36IL12 induced 52% reduction in lesion size and a two-log unit reduction in parasite load. This partial protection correlated with activation of a specific Th1 type of immune response. These protocols could be of interest in the prophylaxis against Leishmania spp. and other parasitic diseases.
Gonzalo
R M
RM
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, 28049 Madrid, Spain.
Rodríguez
J R
JR
Rodríguez
D
D
González-Aseguinolaza
G
G
Larraga
V
V
Esteban
M
M
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan; D003459:Crystallins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007115:Immunization Schedule; D007117:Immunization, Secondary; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018314:Leishmania infantum / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016052:Protozoan Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D038226:zeta-Crystallins
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D003459:Crystallins; D016207:Cytokines; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D038226:zeta-Crystallins; C093139:LACK antigen, Leishmania; D018664:Interleukin-12; D016660:NAD(P)H Dehydrogenase (Quinone)