Visceral leishmaniaisis (VL), caused by Leishmania chagasi in the New World, is a zoonotic disease in which the domestic dog is the principal reservoir host in the peridomestic setting. The sand fly Lutzomyia longipalpis is the principal vector. This proposal is focused on vaccination against canine visceral leishmaniasis with the goal of decreasing the reservoir's infectivity to the sand fly vector, and thus interrupting transmission of this parasite to humans. We hypothesize that even partial protection of dogs will significantly impact the ability of this host to infect the sand fly vector and maintain the transmission of L. chagasi. These proposed studies are an extension of previous work in which we have i) defined the rate of enzootic transmission of L. chagasi within an endemic area, ii) characterized the relationship between the clinical and parasitological status of L. chagasi infected dogs and their infectivity to sand flies, iii) identified a multi-component DNA vaccine that induces a protective immune response in a murine model of VL, and iv) developed canine cytokine DNA constructs for use as vaccine adjuvants. We will determine the optimal route of vaccine delivery of the DNA vaccine and if co-delivery of cytokine DNA can have an adjuvant effect in the canine vaccine model. The protective efficacy of the multi- component vaccine will be tested in parallel by: i) experimental challenge of immunized and control dogs with Lu. longipalpis-derived metacyclic promastigotes, and ii) natural challenge by exposure to naturally infected Lu. longipalpis in an endemic area. The primary efficacy endpoint will be a reduction in the infectivity of the vaccinated dogs to laboratory-reared sand flies. The secondary endpoints for vaccine efficacy will be a reduction in clinical disease and parasite burden in the vaccinated compared to unvaccinated dogs. Successful vaccination of dogs in an endemic could reduce both enzootic (among the canine reservoir) and zoonotic (from the canine reservoir to humans) transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048823-02
Application #
6497391
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Hall, B Fenton
Project Start
2001-02-01
Project End
2004-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
2
Fiscal Year
2002
Total Cost
$313,090
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Travi, Bruno L; Osorio, Elvia Yaneth; Saldarriaga, Omar A et al. (2009) Clinical, parasitologic, and immunologic evolution in dogs experimentally infected with sand fly-derived Leishmania chagasi promastigotes. Am J Trop Med Hyg 81:994-1003
Saldarriaga, Omar A; Travi, Bruno L; Melby, Peter C (2006) Quantification of canine cytokines using real time reverse transcriptase polymerase chain reaction. Biomedica 26 Suppl 1:254-63
Saldarriaga, Omar A; Travi, Bruno L; Park, Won et al. (2006) Immunogenicity of a multicomponent DNA vaccine against visceral leishmaniasis in dogs. Vaccine 24:1928-40
Saldarriaga, Omar A; Perez, Luis E; Travi, Bruno L et al. (2006) Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA. Vet Immunol Immunopathol 110:377-88
Melby, Peter C (2002) Vaccination against cutaneous leishmaniasis: current status. Am J Clin Dermatol 3:557-70
Melby, Peter C (2002) Recent developments in leishmaniasis. Curr Opin Infect Dis 15:485-90