Abstract
An attenuated line of Leishmania infantum (L. infantum H-line) has been established by culturing promastigotes in vitro under gentamicin pressure. A vaccine trial was conducted using 103 naive dogs from a leishmaniosis non-endemic area (55 vaccinated and 48 unvaccinated) brought into an endemic area of southeast Iran. No local and/or general indications of disease were observed in the vaccinated dogs immediately after vaccination. The efficacy of the vaccine was evaluated after 24 months (4 sandfly transmission seasons) by serological, parasitological analyses and clinical examination. In western blot analysis of antibodies to L. infantum antigens, sera from 10 out of 31 (32.2%) unvaccinated dogs, but none of the sera from vaccinated dogs which were seropositive at >100, recognized the 21 kDa antigen of L. infantum wild-type (WT). Nine out of 31 (29%) unvaccinated dogs, but none of vaccinated dogs, were positive for the presence of Leishmania DNA. One out of 46 (2.2%) vaccinated dogs and 9 out of 31 (29%) unvaccinated dogs developed clinical signs of disease. These results suggest that gentamicin-attenuated L. infantum induced a significant and strong protective effect against canine visceral leishmaniosis in the endemic area.
Highlights
Leishmania infantum (L. infantum) is a causative agent of visceral leishmaniasis (VL), which is a severe and frequently lethal protozoan disease of humans and dogs
We previously reported that a cultured attenuated line of L. infantum, identified as L. infantum H-line, was selected by culturing promastigotes in vitro under pressure of gentamicin [11]
L. infantum H-line is more susceptible to oxidative stress, and a change in thiol-redox metabolism in this line may explain its loss of virulence [15]
Summary
Leishmania infantum (L. infantum) is a causative agent of visceral leishmaniasis (VL), which is a severe and frequently lethal protozoan disease of humans and dogs. Comparative proteomics profiling of the attenuated line identified key changes in parasite thiol-redox metabolism [15]. Thiol-redox metabolism is crucial for Leishmania which is exposed to an oxidative burst when they encounter their mammalian macrophage host cell [16]. L. infantum H-line is more susceptible to oxidative stress, and a change in thiol-redox metabolism in this line may explain its loss of virulence [15]. The attenuated line failed to spread to, and within, the visceral organs of BALB/c mice and dogs over a 12 week observation period [17]. Immunohistochemical investigation showed no parasites in the popliteal lymph node (PLN) of immunized dogs whereas there were parasites in the PLN of 60%
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