A transfollicular nanovaccine against leishmaniasis

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$600,000.00
Award Year:
2011
Program:
SBIR
Phase:
Phase I
Contract:
1R43AI096605-01
Award Id:
n/a
Agency Tracking Number:
R43AI096605
Solicitation Year:
2011
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
A169, ASTeCC Bldg.,145 Graham Avenue, LEXINGTON, KY, 40506-0286
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
808379072
Principal Investigator:
PAIMANGHOROGHCHIAN
(267) 259-1086
ppg@vindicopharma.com
Business Contact:
ERICOSTERTAG
(267) 259-1086
ostertag@vindicopharma.com
Research Institute:
Stub




Abstract
DESCRIPTION (provided by applicant): The World Health Organization estimates that over 350 million people are at risk of developing leishmaniasis and infection prevalence is 14 million people in the world. Annually, 2 million people are infected with Leishmania species and 270,000 will die. Leishmaniasis is one of the most important parasitic diseases affecting the U.S. military today, with over 2500 U.S. military personnel diagnosed with cutaneous leishmaniasis (CL). Current non-immunization based treatments are variably effective, highly toxic, expensive, and there are no vaccines in clinical use. Significant evidence has supported the role of the immune system in controlling Leishmania infection. Thus, a vaccination remains an attractive disease prevention strategy. Two significant scientific knowledge gaps must be addressed: 1) a vaccine that can access the skin resident dendritic cells (DCs), and 2) the identification of Leishmania antigens that are biologically relevant in humans. Needle based vaccinesbypass these immunopotent skin cells. The long-term objective of this proposal is to develop a nanoscale polymersome-based vaccine that delivers an antigen and adjuvant to skin dendritic cells through transfollicular immunization (TFI). We will characterize the feasibility of integrating the Toll-like receptor 7/8 agonist resiquimod (RSQ) into the polymersome membrane and encapsulating a model Leishmania antigen, Leishmania homolog of receptors for activated C kinase (LACK), into the aqueous core. We willthen evaluate its functional properties in generating a TH1-type cytokine profile and functional cytotoxic CD8+ T cells in vivo. We hypothesize that co-encapsulation of LACK and RSQ into the nanovaccine can be achieved in a stepwise manner and that the resulting nanovaccine will penetrate the follicle and activate skin DCs. We also hypothesize that the topical administration of this nanovaccine will induce a LACK-specific T cell response. Finally, we hypothesize that this nanovaccine will protect against challenge with a visceral Leishmania strain in a hamster model. AIM 1 Construct a nanovaccine encapsulating the antigen LACK and TLR7/8 agonist RSQ (LACK/RSQ-NPS). AIM 2 Determine the optimal physicochemical properties of LACK/RSQ-nanovaccine to penetrate the follicular duct, activate skin DCs, and induce a LACK-specific adaptive immune response. AIM 3 Determine if the LACK/RSQ-nanovaccine induces protective immune responses in vivo. We anticipate the data generated from this proposal will result in a commercially viable topical nanovaccine that can access skin DCs via the transfollicular route. The NIAID supports basic, preclinical, and clinical research on immune-mediated diseases such as leishmaniasis and the development of effective vaccines. The aims proposed in this SBIR Phase I program are consistent with the mission statement of the NIAID. PUBLIC HEALTH RELEVANCE: The World Health Organization estimates that over 350 million people are at risk of developing leishmaniasis and infection prevalenceis 14 million people in the world. Annually, 2 million people are infected with Leishmania species and 270,000 will die. Leishmaniasis is one of the most important parasitic diseases affecting the U.S. military today. We plan to develop a nanovaccine against Leishmania that delivers the vaccine payload through the hair follicle duct to stimulate skin immune cells, all without a needle. This major advance in Leishmania vaccine design may provide the first effective vaccine against Leishmania and would create biotechnology jobs in the US via US military contracts and international government contracts in countries suffering from leishmaniasis.

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government