title: 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.
authors.affiliation: Instituto de Microbiologia Prof. Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, PO Box 68040, CEP 21941-590, Rio de Janeiro, Brasil.
authors.forename: F N
authors.initials: FN
authors.lastname: Santos
authors.forename: G P
authors.initials: GP
authors.lastname: Borja-Cabrera
authors.forename: L M
authors.initials: LM
authors.lastname: Miyashiro
authors.forename: J
authors.initials: J
authors.lastname: Grechi
authors.forename: A B
authors.initials: AB
authors.lastname: Reis
authors.forename: M A B
authors.initials: MA
authors.lastname: Moreira
authors.forename: O A
authors.initials: OA
authors.lastname: Martins Filho
authors.forename: M C R
authors.initials: MC
authors.lastname: Luvizotto
authors.forename: I
authors.initials: I
authors.lastname: Menz
authors.forename: L M
authors.initials: LM
authors.lastname: Pessôa
authors.forename: P R
authors.initials: PR
authors.lastname: Gonçalves
authors.forename: M
authors.initials: M
authors.lastname: Palatnik
authors.forename: C B
authors.initials: CB
authors.lastname: Palatnik-de-Sousa
mesh_terms: D000818:Animals; D016054:DNA, Protozoan; D004285:Dogs; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000628:therapy*; D016052:Protozoan Vaccines / Q000276:immunology*; D012503:Saponins / Q000737:chemistry*; D013997:Time Factors
chemical_list: D016054:DNA, Protozoan; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D012503:Saponins