Field trial of efficacy of the Leish-tec® vaccine against canine leishmaniasis caused by Leishmania infantum in an endemic area with high transmission rates

Abstract

BackgroundBecause domestic dogs are reservoir hosts for visceral leishmaniasis (VL) in Brazil, one of the approaches used to reduce human disease incidence is to cull infected dogs. However, the results of controlled intervention trials based on serological screening of dogs and killing of seropositive animals are equivocal. A prophylactic vaccine to protect dogs from being infectious to the sand fly vector could be an effective strategy to provide sustained control. Here, we investigated whether a currently licensed commercial subunit rA2 protein–saponin vaccine (Leish-tec®) had an additional effect to dog culling on reducing the canine infectious populations.Methodology/Principal findingsThis prospective study was conducted in an L. infantum highly endemic area of southeast Brazil. At the onset of the intervention, all of the eligible dogs received through subcutaneous route a three-dose vaccine course at 21-day intervals and a booster on month 12. For the purpose of comparison, newly recruited healthy dogs were included as the exposed control group. To ascertain vaccine-induced protection, dogs were screened on clinical and serological criteria every 6 months for a 2-year follow-up period. Antibody-based tests and histopathological examination of post-mortem tissue specimens from euthanized animals were used as a marker of infection. The standardized vaccine regime, apart from being safe, was immunogenic as immunized animals responded with a pronounced production of anti-A2-specific IgG antibodies. It should be noted the mean seroconversion time for infection obtained among immunized exposed dogs (~ 18 months), which was twice as high as that for unvaccinated ones (~ 9 months). After two transmission cycles completed, the cumulative incidence of infection did differ significantly (P = 0.016) between the vaccinated (27%) and unvaccinated (42%) dogs. However, the expected efficacy for the vaccine in inducing clinical protection was not evident since 43% of vaccine recipients developed disease over time. Our estimates also indicated that immunoprophylaxis by Leish-tec® vaccine in addition to dog culling might not have an impact on bringing down the incidence of canine infection with L. infantum in areas of high transmission rates.Conclusions/SignificanceLeish-tec® as a prophylactic vaccine showed promise but needs to be further optimized to be effective in dogs under field conditions, and thereby positively impacts human incidence.

The Delay in the Licensing of Protozoal Vaccines: A Comparative History

“…In fact, the incidence of canine VL was 42% in controls and 27% in vaccinated dogs (122). Furthermore, 43% of the vaccinated dogs developed the disease over time, and seroconversion was higher in vaccinated dogs than in controls (122).…”

“…When parasitologically and xenodiagnosis-positive cases were considered, vaccine efficacy was 58.1% (121). While the first field trial of Leishtec R was performed in a low infective pressure area, a second Phase III trial was run in a high transmission rate area, and the vaccine efficacy was only 35.7% (122). In fact, the incidence of canine VL was 42% in controls and 27% in vaccinated dogs (122).…”

“…While the first field trial of Leishtec R was performed in a low infective pressure area, a second Phase III trial was run in a high transmission rate area, and the vaccine efficacy was only 35.7% (122). In fact, the incidence of canine VL was 42% in controls and 27% in vaccinated dogs (122). Furthermore, 43% of the vaccinated dogs developed the disease over time, and seroconversion was higher in vaccinated dogs than in controls (122).…”

“…Therefore, in contrast to Leishmune R , which showed 76-80% efficacy based on strict end-points (deaths and clinical cases) (100,101) and promoted the decrease of canine and human incidence of VL in areas of high infective pressure (77), the second field assay of Leishtec R showed that, when combined with dog culling, Leishtec R may not reduce the canine incidence of leishmaniasis in areas of high transmission and may have no impact on the human incidence of the disease (122). A recent study on owned hunting dogs infected with L. (L.) infantum showed that, if used for immunotherapy, Leishtec R gave a 25% reduction in the risk of progression to clinical symptoms and a 70% reduction in mortality (123).…”

Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?

“…Ribosomal proteins (e.g., P0), metabolic enzymes (e.g., TPI), stress-related proteins (e.g., HSP), antioxidant-machinery components (e.g., TPR), and even hypothetical proteins ( Table 1) are found among them. One of these candidates, L. donovani A2, is today a licensed veterinary vaccine against leishmaniasis in Brazil-LeishTec ® (that needs however to be optimized, according to a recent efficacy field trial performed in an endemic area with high transmission rates [92]). In the past few years, the development of vaccine candidates against leishmaniasis became more refined and rationale based, following the trends of twenty-first-century vaccinology [93].…”