Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial

Angela Toepp Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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Mandy Larson Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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Tara Grinnage-Pulley Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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Carolyne Bennett Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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Michael Anderson Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;

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Molly Parrish Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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Hailie Fowler Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;

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Geneva Wilson Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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Katherine Gibson-Corely Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa;

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Radhika Gharpure Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

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Caitlin Cotter Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

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Christine Petersen Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa;
Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, Iowa;

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In Leishmania infantum–endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

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Author Notes

Address correspondence to Christine Petersen, Department of Epidemiology, College of Public Health, University of Iowa, S429 CPHB, 145 N. Riverside Dr., Iowa City, IA 52241. E-mail: christine-petersen@uiowa.edu

Authors’ addresses: Angela Toepp, Mandy Larson, Molly Parrish, and Geneva Wilson, College of Public Health, University of Iowa, Iowa City, IA, E-mails: angela-schneider@uiowa.edu, maklarson@gmail.com, molly-parrish@uiowa.edu, and geneva-wilson@uiowa.edu. Tara Grinnage-Pulley, National Cancer Institute, Frederick, MD, E-mail: tara.grinnage-pulley@nih.gov. Carolyne Bennett and Caitlin Cotter, Centers for Disease Control and Prevention, Decatur, GA, E-mails: nuw8@cdc.gov and caitlincotter@gmail.com. Michael Anderson, Center for State and Territorial Epidemiologists, Atlanta, GA, E-mail: manderson@cste.org. Hailie Fowler, Integrated DNA Technologies, Coralville, IA, E-mail: hflowler@idtdna.com. Radhika Gharpure, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, E-mail: radhika.gharpure@gmail.com. Christine Petersen, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, and Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, IA, E-mail: christine-petersen@uiowa.edu.

These authors contributed equally to this work.

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