Development and clinical trial of a novel DNA vaccine as immunotherapy during canine Leishmaniasis

Background:Visceral Leishmaniasis (VL) is a zoonotic disease caused byLeishmaniainfantumin the Mediterranean area. Dogs are the main reservoir ofLeishmaniainf antumparasites. Disease management represents a serious problem, since anti-Leishmaniadrugs have limited efficacy in both symptomatic and asymptomatic dogs, which are infective to phlebotomine vectors. In many tropical and sub-tropical countries the development of a safe and easily-available vaccine has high priority. DNA vaccines represent one of the most recent innovations in the field of immunization.Findings:This study aimed to evaluate the effect of a DNA vaccine based on twoLeishmaniaantigens (Cpb1, PO) in leishmaniotic dogs. Twelve leishmaniotic dogs from a Leishmaniasis-endemic area (Naples, Italy) received three consecutive injections of DNA vaccine at 15-days intervals. Another group of five leishmaniotic dogs received the same amount of pVAX-1 without the coding sequences ofLeishmaniaantigens.LeishmaniaDNA load, INFγ, IL-4 mRNA expression levels and clinical parameters were tested before and after the therapy, every 3 months for a period of 12 months.Analysis of the data in the vaccinated dogs showed: i) a decreaseLeishmaniaDNA load in lymph node samples, ii) an increase of INFγ and IL-4 mRNA expression levels in PBMC samples. All vaccinated dogs also showed an improvement in the clinical symptoms.Conclusion:Our results show that the vaccine developed in this study may represent a useful tool in the treatment of leishmaniotic dogs. However, since the duration of positive effects is limited in time, further trials are needed to evaluate the effectiveness of immunotherapy alone or in association with conventional therapy.