Leish-111f

Immunotherapy of canine visceral leishmaniasis (CVL) may provide an alternative to both marginally effective chemotherapy and undesired euthanasia of infected dogs and could have a great impact not only on animal welfare, but also on control of human disease. Therefore, we examined the potential immunotherapeutic efficacy of the subunit vaccine Leish-111f+MPL-SE, which has undergone rigorous preclinical testing and been demonstrated safe in human clinical trials. Two separate trials were performed in Salvador, Brazil, to evaluate the vaccine for therapeutic efficacy against CVL caused by natural infection: an Open Trial and a Blinded Trial. In the Open Trial 59 dogs with clinically active CVL were sequentially allocated to four groups: group 1 received Leish-111f+MPL-SE; group 2 was treated with Glucantime; group 3 received a combination of the vaccine and Glucantime; and group 4 was given no treatment. At the 6-month assessment, the 13 non-treated dogs had either died or showed no clinical improvement. In contrast, most dogs in groups 1-3 showed initial improvement (100%, 80%, and 92%, respectively). Upon evaluation for a mean of 36 months after therapy, the following cure rates were observed: 75% for group 1 dogs (exact 95% confidence interval [CI] 43-95%), 64% for group 2 dogs (exact 95% CI 31-89%), and 50% for group 3 dogs (exact 95% CI 19-81%). Therapeutic efficacy of the Leish-111f+MPL-SE vaccine was reconfirmed in a subsequent Blinded Trial. The vaccine was effective for mild cases of CVL and was compromised in dogs with severe disease. Although further studies are required to understand mechanisms of action, the Leish-111f+MPL-SE vaccine is a promising tool to control VL in both dogs and humans.

The mucosal vaccination is a non-invasive alternative approach for not only mucosal pathogens but also parenteral pathogens, since it induces both mucosal and systemic immunoreactions. The purpose of this study was to evaluate the application of intranasal (i.n.) immunization with a recombinant leishmanial protein against Leishmania infection. BALB/c mice were i.n. administered 1-3 times with Leish-111f plus cholera toxin (CT) adjuvant (Leish-111f/CT). Splenocytes from i.n. immunized mice produced high level of IFN-gamma but not IL-4 in response to Leish-111f. When infected with 1x10(6) of Leishmania major promastigotes 2 weeks after the final administration, lesion development was completely controlled in all mice i.n. administered with Leish-111f/CT. Mice i.n. administered with Leish-111f alone showed neither cytokine productions nor lesion control even after 6 administrations, suggesting the importance of CT adjuvant. This report demonstrated for the first time that i.n. administration of a recombinant leishmanial protein induces Th1 type immunity and protects mice from Leishmania infection.