Journal Article

Randomized, controlled, double-blinded field trial to assess Leishmania vaccine effectiveness as immunotherapy for canine leishmaniosis

Fowler, Hailie, Hinman, Jessica, Cotter, Caitlin, Toepp, Angela, Parrish, Molly, Kontowicz, Eric, Saucier, Jill, Petersen, Christine, Gharpure, Radhika, Larson, Mandy, Beeman, Marvin, Bennett, Carolyne, Anderson, Michael, Jefferies, Jane, Buch, Jesse, Grinnage-Pulley, Tara, Anderson, Bryan, Leal-Lima, Adam, Tyrrell, Phyllis, Wilson, Geneva

2018

Overview

•Blinded clinical field trial.•Anti-Leishmania vaccine as immunotherapy significantly reduced clinical progression.•Vaccine decreased mortality in Leishmania infantum-infected, healthy, dogs. Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants, Immunologic - therapeutic use / Age / Animals / Antibodies, Protozoan - blood / Antigens / Antigens, Protozoan - immunology / Asymptomatic Infections - therapy / Brazil / Canine / disease models / Disease Progression / Disease Reservoirs - veterinary / Dog Diseases - parasitology / Dog Diseases - therapy / Dogs / Dogs - immunology / Dogs - parasitology / field experimentation / Health promotion / humans / Hunting / hunting dogs / Immunotherapy / Immunotherapy - veterinary / Infections / Leishmania / Leishmania infantum / Leishmaniasis Vaccines - therapeutic use / Leishmaniasis, Visceral - therapy / Leishmaniasis, Visceral - veterinary / Mediterranean region / Mortality / Parasitic diseases / placebos / Proteins / Public health / Random Allocation / Randomization / Reduction / Tropical diseases / Vaccination / Vaccination - veterinary / Vaccine efficacy / Vaccines / Vector-borne diseases / Vectors (Biology) / Visceral leishmaniasis / Zoonoses / Zoonoses - parasitology