Project Details for

Completed Research Projects

Title: Vaccination Against Visceral Leishmaniasis with a Multi-epitope Vaccine
Synopsis: This project looked at the next steps toward developing a human vaccine against leishmaniasis.
Overall Summary: Visceral leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a severe disease that affects millions of people around the world. In humans, recovery from either clinically apparent or sub-clinical infection with L. donovani appears to confer immunity to active visceral disease. This epidemiological observation indicates that prophylactic immunization could contribute to the control of this disease. However, an effective vaccine is not currently available. For the last several years this laboratory has worked to identify vaccine candidates to prevent this disease. Recently identified a multi-component DNA vaccine that encodes several L. donovani histone antigens that effectively immunizes mice against parasite challenge. This exciting finding is the first step, but there are a number of questions related to the mechanisms of this vaccine-induced immunity and its optimization that must be answered.
Overall Project Objective: For this project the designed experiments will take the next step forward toward the ultimate goal of vaccinating humans to prevent visceral leishmaniasis. The initial experiments will identify the specific antigenic epitopes that induce protective immunity. We will then determine and compare the immunogenicity and protective efficacy of if second generation" histone DNA-based and protein/peptide-based vaccines in both non-permissive (moderately susceptible BALB/c mice) and permissive (highly susceptible Syrian hamster) challenge models. We will then determine the mechanisms responsible for the induction and effector phases of the vaccine-induced immunity.
Results to Date: None to date.
Project: VA-99
Agency: Department Of Veterans Affairs
Location: VAMC San Antonio
P.I. Name: Peter Melby
Status: Complete
Study Start Date: April 01, 2002
Estimated Completion Date: March 31, 2007
Specific Aims: The short-term objectives of the project are: Short-term Objective 1: To identify the T cell antigenic epitopes responsible for the protective immune response to the histone antigens (year 1 and 2). Short-term Objective 2: To determine the immunogenicity and efficacy of a synthetic multiepitope DNA vaccine in non-permissive and permissive models of visceral leishmaniasis (years 2, 3, and 5). Short-term Objective 3: To determine the effector mechanisms responsible for histone DNA and protein vaccine-induced protective immunity (year 4 and 5).
Methodology: Hypothesize a synthetic multi-epitope vaccine (either in DNA or protein form) that contains multiple antigenic T cell epitopes derived from the five different L. donovani histone proteins will be significantly more effective than the "first generation" parent DNA vaccine.
Publications:
No Publications at this time...