DOYLESTOWN, PA, United States
DOYLESTOWN, PA, United States

Time filter

Source Type

Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF) are significant global public health problems and understanding the overall immune response to infection will contribute to appropriate management of the disease and its potentially severe complications. Live attenuated and subunit vaccine candidates, which are under clinical evaluation, induce primarily an antibody response to the virus and minimal cross-reactive T cell responses. Currently, there are no available tools to assess protective T cell responses during infection or post vaccination. Herein, we report novel, naturally processed and presented MHC class I restricted epitopes, a subset of which binds to and activates T cells in both an HLA-A2 and HLA-A24 restricted manner. We show that epitope specific T cells can be activated in vivo in transgenic mice and in vitro in seropositive and seronegative individuals and that these T cells are functional, recognizing peptide pulsed and dengue virus infected cells in a pro-inflammatory and cytotoxic manner. These epitopes have potential as new informational and diagnostic tools to characterize T cell immunity in Dengue virus (DV) infection, and may serve as a universal vaccine candidate complementary to current vaccines in trial.


Patent
Midatech and Immunotope, Inc. | Date: 2012-09-07

The present invention provides a vaccine for the prophylactic or therapeutic treatment of a tumour in a mammalian subject, as well as methods of using the vaccine, including in treatment of tumours and in generating a CTL response. The vaccine comprises a plurality of nanoparticles and a pharmaceutically acceptable carrier, salt or diluents. The nanoparticles comprise a core comprising a metal and/or a semiconductor atom; and a corona comprising a plurality of ligands covalently linked to the core, wherein at least a first ligand of said plurality comprises a carbohydrate moiety that is covalently linked to the core via a first linker, and wherein at least a second ligand of said plurality comprises an epitopic peptide that is covalently linked to the core via a second linker, said second linker comprising a peptide portion and a non-peptide portion, wherein said peptide portion comprises the sequence X_(1)X_(2)Z_(1), wherein X_(1 )is an amino acid selected from A and G; X_(2 )is an amino acid selected from A and G; and Z_(1 )is an amino acid selected from Y and F, and wherein said epitopic peptide forms at least a portion of or is derived from a Tumour-Associated Antigen (TAA).


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 2.97M | Year: 2012

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.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 388.35K | Year: 2013

DESCRIPTION (provided by applicant): The overall goal of this application is to develop and validate a potential biomarker based assay to determine if it can be used as a noninvasive test to detect the stage of hepatic fibrosis and to predict fibrosis progression in HIV/HCV co-infected patients. Significant fibrosis and cirrhosis are premalignant conditions that greatly increase the risk of the development of hepatocellular carcinoma (HCC). We have recently reported increases in a glycoform of an antibody directed toward many gram negative and positive bacteria (lectin-reactive anti-Gal IgG, LRAGG) in patients with liver fibrosis. LRAGG has shown superior discriminatory ability, as compared to clinically available non-invasive markers of liver fibrosis, i.e.Fibrosure/Fibrospect, in differentiating mild fibrosis (not a pre-malignant conditio) from advanced fibrosis (a pre- malignant condition). The Fibrosure assay, and other algorithm based tests use a combination of several serum biomarkers and patented algorithms to measure fibrogenesis of the liver. Due to their complexity and limited available data in distinguishing stages of fibrosis, especially pre- malignant conditions, these tests are considered in the clinical diagnostic field as investigational andmedically not necessary. Therefore, simple easy to use high sensitive assays are needed to accurately detect and classify fibrosis in HIV/HCV co- and mono-infected patients. Based on the recent reports that have shown increased peripheral levels of bacterial endotoxin in patients with hepatic fibrosis, we hypothesize that chronic exposure to bacterial products, such as endotoxin, might occur in patients with advanced liver disease due to HCV or HCV/HIV co- infection, and promote increased production of LRAGG. Changes in glycosylation on LRAGG as hepatic fibrosis progresses interfere with normal bactericidal processes. The outcome of enhanced bacterial exposure is stimulation and perpetuation of the inflammatory and fibrogenic pathways. In this phase I proofof concept study, we propose to assess whether this biomarker has potential utility as noninvasive indicator of the stage of fibrosis as well as their utility as predictive marker for fibrosis progression and better performers than the existing fibrosis tests using archived serum samples. In phase II, we will collaborate with our clinical collaborators and perform prospective studies using this biomarker. Since we have accumulated large datasets in HCV mono-infected patients, this study will be conducted in HIV/HCV co- and HCV mono-infected patients undergoing clinical evaluation to assess the histological severity of HCV- associated liver disease. Success of this proposal will determine the feasibility of using LRAGG as a novel biomarker for liver fibrosisclassification, and form a strong foundation for developing a clinical diagnostic and prognostic test. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The over-all goal of this proposal is to develop a novel biomarker based non- invasive liver fibrosis diagnostic test to distinguish mild fibrosis (not a pr-malignant condition) from advanced fibrosis (a pre-malignant condition) as well as to predict fibrosis progression in patients with HIV/HCV co-infection. In our research, we have identifiedincreases in a glycoform of an antibody directed toward many gram negative and positive bacteria (lectin-reactive anti-Gal IgG, LRAGG) in patients with liver fibrosis. In this application we propose to validate the ability of this promising biomarker to differentiate among patients with different stages of fibrosis and demonstrate superior performance of this assay compared to the existing complex, technically challenging Fibrotest assay in liver fibrosis classification ad progression. Successful completionof this project will generate a simple and non-invasive test for liver fibrosis applicable to infection induced liver disease.


The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of Hepatitis B virus (HBV) infection, and discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against HBV infection. The peptide and/or proteins of the invention may be used as a therapeutic drug to stimulate the immune system to recognize and eliminate HBV infection in infected cells or as a vaccine for the prevention of disease.


The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as lung carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against lung and other cancers.


The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as pancreatic carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against pancreatic and other cancers.


Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHR) are significant global public health problems and understanding the overall immune response to infection will contribute to appropriate management of the disease and its potentially severe complications. Live attenuated and subunit vaccine candidates, which are under clinical evaluation, induce primarily an antibody response to the virus and minimal cross-reactive T cell responses. Currently, there are no available tools to assess protective T cell responses during infection or post vaccination. The present invention incorporates immunoproteomics to uncover novel HLA-A2 specific epitopes derived from Dengue Virus (DV)-infected cells. These epitopes are conserved with epitope-specific CTLs cross-reacting against all four DV serotypes. These epitopes have potential as new informational and diagnostic tools to characterize T cell immunity in Dengue virus (DV) infection, and serves as a universal vaccine candidate complementary to current vaccines.


The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as ovarian carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against cancer.


The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as ovarian carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against cancer.

Loading Immunotope, Inc. collaborators
Loading Immunotope, Inc. collaborators