A nanoparticle-based vaccine against leishmaniasis

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$599,977.00
Award Year:
2011
Program:
STTR
Phase:
Phase I
Contract:
1R41AI091234-01A1
Award Id:
n/a
Agency Tracking Number:
R41AI091234
Solicitation Year:
2011
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-124
Small Business Information
BOX 8175, NEW HAVEN, CT, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
142406110
Principal Investigator:
DIANEMCMAHON PRATT
(203) 785-4481
diane.mcmahon-pratt@yale.edu
Business Contact:
MARTINMATTESSICH
(203) 393-9439
mmattessich@L2dx.com
Research Institute:
YALE UNIVERSITY

YALE UNIVERSITY
47 COLLEGE STREET, STE 203 PO BOX 208047
NEW HAVEN, CT, 06520-8047
() -

Abstract
DESCRIPTION (provided by applicant): We propose to develop a recombinant subunit vaccine against cutaneous leishmaniasis. This vaccine will incorporate two protein antigens, TSA/TryP and P-4. Both antigens are highly conserved among Leishmania species, arerecognized by T cells of human patients, and confer protection against a live challenge in murine model studies. We expect that immunization using PLGA nanoparticles together with these two proteins will confer protection against disease caused by many ofthe Leishmania species. Recombinantly expressed TSA/TryP and P-4 proteins will be formulated into PLGA nanoparticles containing one of two adjuvants, namely a CpG oligonucleotide and/or monophosphoryl lipid A (MPLA). Different formulations will be evaluated for immunogenicity and duration of the immune response (memory) in mice. We expect that proteins encapsulated in PLGA particles will elicit long-lasting immune responses. Protection against Leishmania has been shown to be mediated primarily by T-cells,and in particular CD4+/CD8+ T-cells double-positive or triple-positive for IL-2, TNFalpha, and IFN-gamma. We will select the two formulations eliciting the highest proportion responding CD4/CD8 T cells. These two formulations will then be tested for efficacy in two murine models of leishmaniasis. The first model is a challenge with L. major, the main species responsible for leishmaniasis in the Old World. The second model is an infection with L. (Viannia) panamensis, a model for New World leishmaniasis andpossibly a more stringent test of vaccine efficacy. In Phase II of this project, we anticipate testing the efficacy of the most promising formulation in non-human primate models of leishmaniasis. PUBLIC HEALTH RELEVANCE: Leishmaniasis is a serious parasitic disease endemic in many subtropical countries. It is estimated that more than 12 million individuals are infected globally and 1-2 million contract the disease annually. Further, hundreds of US military personnel developed leishmaniasis after being deployed in Iraq and Afghanistan; some cases have also occurred in the Southern United States. We propose to develop a vaccine to prevent this disease.

* information listed above is at the time of submission.

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