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

Abstract

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.