Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched-Leishmune® vaccine

Abstract

In order to assess the immunotherapeutic potential on canine visceral leishmaniasis of the Leishmune vaccine, formulated with an increased adjuvant concentration (1mg of saponin rather than 0.5mg), 24 mongrel dogs were infected with Leishmania (L.) chagasi. The enriched-Leishmune vaccine was injected on month 6, 7 and 8 after infection, when animals were seropositive and symptomatic. The control group were injected with a saline solution. Leishmune-treated dogs showed significantly higher levels of anti-FML IgG antibodies (ANOVA; p<0.0001), a higher and stable IgG2 and a decreasing IgG1 response, pointing to a TH1 T cell mediated response. The vaccine had the following effects: it led to more positive delayed type hypersensitivity reactions against Leishmania lysate in vaccinated dogs (75%) than in controls (50%), to a decreased average of CD4+ Leishmania-specific lymphocytes in saline controls (32.13%) that fell outside the 95% confidence interval of the vaccinees (41.62%, CI95% 43.93-49.80) and an increased average of the clinical scores from the saline controls (17.83) that falls outside the 95% confidence interval for the Leishmune immunotherapy-treated dogs (15.75, CI95% 13.97-17.53). All dogs that received the vaccine were clustered, and showed lower clinical scores and normal CD4+ counts, whereas 42% of the untreated dogs showed very diminished CD4+ and higher clinical score. The increase in clinical signs of the saline treated group was correlated with an increase in anti-FML antibodies (p<0.0001), the parasitological evidence (p=0.038) and a decrease in Leishmania-specific CD4+ lymphocyte proportions (p=0.035). These results confirm the immunotherapeutic potential of the enriched-Leishmune vaccine. The vaccine reduced the clinical symptoms and evidence of parasite, modulating the outcome of the infection and the dog's potential infectiosity to phlebotomines. The enriched-Leishmune vaccine was subjected to a safety analysis and found to be well tolerated and safe.

Vaccine candidates for leishmaniasis: A review

“…Various studies have been carried out in dogs using FML antigen in combination with saponin as an adjuvant and encouraging results have been observed in almost all cases [161][162][163][164][165][166]. Vaccination with FML antigen conferred effective protection with increased level of IgG2a and 79-100% delayed type hypersensitivity (DTH) response in experimentally infected [163] and naturally exposed dogs [161].…”

“…However, immunization with Leishmune®, a licensed formulation of FML and saponin (1 mg), led to more positive delayed type hypersensitivity reactions, significantly higher levels of anti-FML IgG antibodies, a higher and stable IgG2 and a decreasing IgG1 response, skewing to a Th1 T cell mediated response. The vaccine reduced the clinical symptoms and evidence of parasite, modulating the outcome of the infection and the dog's potential infectiosity to phlebotomines [164]. Borja-Cabrera et al [165] monitored the Leishmune®-induced immunogenicity in healthy seronegative and untreated exposed dogs for 2 years.…”

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

“…Saponin-based adjuvants have the ability to modulate the cell-mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity [19]. QS21 fraction of saponin in combination with FML (Leishmune ® ) has been registered in Brazil for immunization in dogs and induced significant protection in various trials [20][21][22]. Liposomes are versatile and robust delivery systems known for induction of humoral and cell-mediated immune responses.…”

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“…These results suggest an effect of vaccination on transmission to sandflies. The Leishmune ® vaccine, which is commercialised in Brazil, has also been reported to reduce transmission of L. infantum from dogs to sandfly vectors in South America (Saraiva et al, 2006;Santos et al, 2007).…”