Double-Blind Randomized Efficacy Field Trial of Alum Precipitated Autoclaved Leishmania major (Alum-ALM) Vaccine Mixed With BCG Plus Imiquimod Vs. Placebo Control Group

Background: Canine visceral leishmaniasis (CVL) is not only an emerging veterinary concern but also a public health threat in endemic areas. The aim of this study was to assess the efficacy, immunogenicity and safety of two doses of aluminum hydroxide (alum) precipitated Leishmania major (Alum-ALM) mixed with BCG plus imiquimod against CVL. Methods: A total of 560 ownership dogs were serologically tested and 234 healthy dogs with no clinical signs of CVL, no anti-Leishmania antibodies and negative leishmanin skin test were selected and double-blind randomly injected intradermally either with 0.1 ml Alum-ALM (200µg protein) mixed with BCG (2 × 10(6) CFUs) plus imiquimod (121 dogs) or with 0.1 ml of normal saline (113 dogs). Results: The follow-up examinations showed that there was no side effect associated with the vaccination except one case. Strong skin test conversion were seen in vaccinated group (30.3%) compared to the control group (6.6%) at 22-24 weeks after the booster injection (p<0.001). The seroconversion was 16.3% (18/110) in vaccinated group and 26.4% (28/106) in control group after two transmission cycles but the difference was not significant (P=0.095). The efficacy rate based on seroconversion was 40.4 %. Conclusion: Two injections of Alum-ALM mixed with BCG and imiquimod is safe, although decreases the seroconversion rate of CVL, but the overall efficacy was low.