The long-term goal of this research program is to validate in dogs a candidate vaccine against visceral leishmaniasis (VL) for evaluation in future clinical evaluations. We have recently described a powerful and reliable antigen discovery strategy to directly identify microbial vaccine candidate antigens in human bodily secretions. We combined RP-HPLC and mass spectrometry and categorized three distinct Leishmania infantum proteins presumably produced in parasite infected organs (liver/spleen/bone marrow) and excreted in the urine of patients with VL. The hypothesis underlying these studies was that microbial antigens found in vivo in the bodily fluids of the host are potentially effective vaccine candidate molecules because they represent microbial molecules abundantly produced in vivo that can be directly associated with the host defenses. The genes coding for these L. infantum proteins found in the patients'urine have been cloned, and the purified recombinant molecules have been obtained. Mice immunized with these proteins mixed with the adjuvant MPLA-SE developed robust Th1 response. Importantly one of these proteins induced strong protection in these animals after challenged with virulent L. infantum. The next and pragmatic challenge in the clinical translation of these findings is to expand these initial developmental studies and show that this novel molecule induces protective immunity in dogs, which are the ultimate animal model to test vaccine candidates for both human and canine VL.

Public Health Relevance

Visceral Leishmaniasis (VL) remains a major infectious cause of morbidity and mortality worldwide in both humans and dogs. The incidence of the disease remains high and is increasing in many parts of the world. There is no efficacious vaccine to prevent VL and treatment of this disease is difficult and the drugs are toxic. The present project proposes to validate in the dog model of the disease a novel and promising vaccine candidate for assessment in future clinical evaluations against both human and canine VL.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43AI100327-02
Application #
8474693
Study Section
Special Emphasis Panel (ZRG1-IMM-N (12))
Program Officer
MO, Annie X Y
Project Start
2012-05-23
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$300,000
Indirect Cost
Name
Detectogen, Inc.
Department
Type
DUNS #
828352240
City
North Grafton
State
MA
Country
United States
Zip Code
01536