Defining T cell epitopes in Dengue virus infection

Award Information
Agency:
Department of Health and Human Services
Branch:
N/A
Amount:
$2,974,009.00
Award Year:
2012
Program:
SBIR
Phase:
Phase II
Contract:
2R44AI062177-03
Agency Tracking Number:
R44AI062177
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-123
Small Business Information
IMMUNOTOPE, INC.
THE PENNSYLVANIA BIOTECHNOLOGY CENTER, 3805 OLD EASTON ROAD, DOYLESTOWN, PA, -
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
131080983
Principal Investigator
 RAMILA PHILIP
 (215) 489-4955
 rphilip@immunotope.com
Business Contact
 MOHAN PHILIP
Phone: (215) 489-4945
Email: mphilip@immunotope.com
Research Institution
 Stub
Abstract
DESCRIPTION (provided by applicant): There is a well-recognized need to develop vaccines that stimulates humoral immunity as well as a potent T cell immunity in order to achieve protection from infection with pathogens. Although numerous investigations arefocused on developing vaccines that induce protective humoral responses, only a few studies are aimed towards developing specific T cell immunity for various infections, including dengue virus. The critical components for a successful vaccine, that provides protective T cell immunity, are the identity of specific T cell epitopes and an optimized vaccine delivery system that is capable of delivering the antigens and the adjuvants simultaneously. In the phase I of the project, we have successfully identifiedand characterized HLA-A2 (allele representing ~40% of the world population) specific conserved epitopes and have demonstrated the feasibility of epitope based vaccine for dengue infection. In the phase II of this project, we propose to extend the discovery process to identify epitopes specific for HLA- A24, the major HLA allele in Asian population and characterize both the HLA-A2 and A24 epitopes using PBL from dengue virus infected patient cohorts. In addition, we propose to characterize a vaccine formulation of these cross serotype conserved antigenic epitopes in a novel gold glyconanoparticle delivery system that incorporates Toll Like Receptor (TLR) agonist, a promiscuous synthetic T helper peptide from tetanus toxoid and the bacterial mimetic GlcNAc asadjuvants and assess in vitro and in vivo for CTL activation and toxicity to generate preclinical data. At the end of the phase II, we would have necessary preclinical data to file an IND for a pilot phase 0/I clinical evaluation of the muli-epitope-basedvaccine product that induces specific T cell responses against DV infection in HLA-A2 and A24 positive human subjects. PUBLIC HEALTH RELEVANCE: There is a well-recognized need to develop vaccines that stimulates humoral immunity as well as a potent T cell immunity in order to achieve protection from infection with pathogens. Although numerous investigations are focused on developing vaccines that induce protective humoral responses, only a few studies are aimed towards developing specific T cell immunity for various infections, including dengue virus, which causes Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF), a significant global public health problems. The overall goal of this Phase II proposal is to characterize a vaccine formulation of apanel of cross serotype conserved antigenic epitopes in a novel gold glyconanoparticle delivery system for the development of a universal vaccine against dengue infection.

* information listed above is at the time of submission.

Agency Micro-sites

US Flag An Official Website of the United States Government