Heterologous prime-boost vaccination with a non-replicative vaccinia recombinant vector expressing LACK confers protection against canine visceral leishmaniasis with a predominant Th1-specific immune response.
Leishmaniasis caused by Leishmania infantum is a severe endemic disease in the Mediterranean basin, being domestic dogs the main reservoir of the disease that plays a key role in the transmission to humans. Studies on vaccines against canine leishmaniasis, aimed to modify the T cell repertoire, have advanced in recent years. LACK vaccination assays, using protein or DNA vectors, show protection against cutaneous L. major infections by redirecting the early IL-4 responses to a protective Th1 response. The aim of this study was to define the effectiveness and type of immune response in a canine visceral leishmaniasis model of two poxvirus vectors (Western reserve strain, WR and modified vaccinia virus Ankara, MVA) expressing the LACK protein of L. infantum in prime/boost vaccination protocols. The results obtained showed that dog vaccination priming with DNA-LACK followed by a booster with MVA-LACK or rVV-LACK triggered a Th1 type of immune response, leading to protection against canine visceral leishmaniasis. This protection correlated with absence of visceral leishmaniasis symptoms, lower Leishmania-specific antibodies, higher degree of T cell activation in Leishmania-target organs and higher synthesis of Th1 cytokines. In addition, we found that dogs boosted with the non-replicative virus show less VL symptoms and higher degree of T cell activation, providing evidences for a clear advantage of MVA-LACK as a vaccination vector against canine visceral leishmaniasis.
Ramos
I
I
Centro de Investigaciones Biológicas, Spanish Research Council, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Alonso
A
A
Marcen
J M
JM
Peris
A
A
Castillo
J A
JA
Colmenares
M
M
Larraga
V
V
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004283:Dog Diseases / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D004285:Dogs; D005822:Genetic Vectors; D007114:Immunization / Q000662:veterinary; D007117:Immunization, Secondary / Q000662:veterinary; D018314:Leishmania infantum / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control / Q000662:veterinary*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000502:physiology
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D019444:Vaccines, DNA; C093139:LACK antigen, Leishmania