Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 500.00K | Year: 1992
THE PURPOSE OF THIS PROJECT IS TO DEVELOP AN ASSAY SYSTEM WITH HIGH THROUGHPUT THAT IS CAPABLE OF SCREENING THE EFFICIENCY OF POLYNUCLEOTIDE DELIVERY SYSTEMS UNDER VARIOUS CONDITIONS IN TISSUE CULTURE. SEVERAL NOVEL CATIONIC LIPID ANALOGS AND A VARIETY OF LIPID VEHICLE COMPOSITIONS WILL BE QUANTITATIVELY SCREENED FOR FUNCTIONAL DELIVERY AND EXPRESSION OF A REPORTER GENE PRODUCT IN THE PRESENCE AND ABSENCE OF SERUM. THE AIM WILL BE TO IDENTIFY CANDIDATE FORMULATIONS THAT LEAD TO IMPROVED DELIVERY AND EXPRESSION OF GENES IN VIVO. IN ADDITION TO IDENTIFYING CANDIDATE FORMULATIONS FOR IN VIVO DELIVERY OF POLYNUCLEOTIDES, THIS PROJECT WILL RESULT IN INTERIM PRODUCTS WITH SIGNIFICANT SCIENTIFIC AND COMMERCIAL POTENTIAL AS MOLEUCLAR BIOLOGY REAGENTS. THESE PRODUCTS WILL IMPROVE ON THE EXISTING LIPOFECTIN TRANSFECTION REGENT. THE IMPROVED PRODUCT THAT EMERGES FROM THIS PROJECT WILL RESULT IN GREATER IN VITRO TRANSFECTION ACTIVITY AND REDUCEDCELLULAR TOXICITY. IN ADDITION, THE PRODUCT WILL BE TESTED FOR ACTIVITY ON EMBRYONIC STEM CELLS WHICH, IF ACTIVE, COULDFACILITATE THE STUDY OF TRANSGENIC ANIMALS PRODUCED BY HOMOLOGOUS RECOMBINATION USING CATIONIC LIPID-MEDIATED IN VITRO TRANSFECTION INSTEAD OF ELECTROPORATION.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 3.14M | Year: 2005
DESCRIPTION (provided by applicant): Vical Inc. of San Diego, Ca. is the largest GMP manufacturer of plasmid DNA for vaccine clinical trials in the world. We have manufactured GMP plasmid DNA vaccines that are being used or entering clinical trials for HIV (in the US and China), malaria (up to 9 plasmids), Ebola, WNV, and SARS. Vical has undertaken an internal Product Development Program that focuses on the control of CMV viremia and the reduction of CMV disease and associated complications in patients undergoing either hematopoietic cell (HCT) or solid organ transplantation (SOT). A Phase 1 SBIR (R43 AI058386) approved from Feb to July 2004 (originally planned for November 2003 to April 2004) supplied funds to assist us to develop a CMV DNA vaccine and prepare for IND filing. The final milestone for seeking a Phase II SBIR was IND allowance of the vaccine. That milestone was achieved in March 2004. The Phase II SBIR proposal will support that development of the Vical CMV immunotherapeutic vaccine through Phase 1 and Phase 2 trials over the next 3 years of development. Specifically, we plan to: 1) To move the Vical bivalent CMV vaccine with gB and pp65 genes (VCL-CB01) into Phase 1 clinical trials for evaluation of safety and immunogenicity. 2) To study VCL-CB01 in Phase 2 trials in the HCT population to determine potential endpoints for an efficacy trial 3) To develop a second generation trivalent CMV vaccine (VCL-CT01) encoding the gB, pp65, and IE1 genes 4) To advance either VCL-CB01 or VCL-CT01 in the SOT population in conjunction with the Collaborative Antiviral Study Group of the NIH.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 299.62K | Year: 2005
DESCRIPTION (provided by applicant): The overall goal of this Phase I STTR proposal from the University of Washington (UW) and Vical Incorporated is to advance a multivalent, plasmid DNA (pDNA) immunotherapeutic vaccine for HSV-2 through preclinical development up to point of a pre-IND meeting. This proposal will combine the expertise of the UW group, the leading HSV-2 research group in the world, and the capabilities at Vical, one of the largest manufacturers of clinical plasmid DNA (pDNA). The formulated vaccine would contain up to five HSV-2 viral genes that are known to induce CD4+ and cytotoxic CD8+ T cell responses in man. The vaccine would be designed to decrease the shedding of HSV-2 virus, which would be evaluated in the clinical phase by quantitative daily genital shedding measures as a surrogate marker of clinical benefit. An observed decrease in viral burden would be followed by definitive trials that examined the clinical recurrence rate in the vaccine and then the effect on transmission of the disease. This STTR proposal will support our HSV immunotherapeutic vaccine development through: 1) identification of the genes to be included in the vaccine; 2) the design of the specific sequences of those genes; 3) the cloning into a clinical plasmid backbone and evaluation of expression in vitro using novel assay methodology; 4) testing immunogenicity of the individual plasmids; and 5) evaluation of various combinations in vivo. Once the vaccine composition is determined, we will hold a pre-IND meeting to determine the pre-clinical toxicology and safety studies that will be needed. The specific milestone to be reached for moving to Phase II funding by the STTR program will be to have a successful pre-IND meeting that defines the developmental pathway forward into human Phase 1 safety and Phase 2 proof-of principal clinical trials.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 2.00M | Year: 2008
DESCRIPTION (provided by applicant): Herpes simplex viruses infect humans worldwide. In the US, herpes simplex virus type 2 (HSV-2) infects about 17% of adults. Rates are far higher in the developing world, especially in populations with high HIV-1 prev alence. HSV-2 infections are permanent and the virus establishes latency in dorsal root ganglia neurons after infection. Periodic reactivation leads to HSV-2 shedding, although transmitting persons usually do not have symptoms or lesions when they transm it virus. HSV-2 has serious medical consequences including fatal/disabling neonatal infection and infection renders persons twice as susceptible to HIV-1 infection. Therapeutic manipulation of the immune response (immunotherapy) is a good strategy to imp act symptomatic disease, HSV-2 shedding, and ultimately, HSV-2 transmission in the community. Vaccine trials and non-clinical human and animal studies show that cellular immunity controls the duration and severity of HSV lesions. HSV-specific CD8+ T cell s localize to infected ganglia in humans and CD8+ T cell presence correlates with viral clearance. HSV-2 tegument proteins, including those encoded by genes UL46 and UL47 are prominent CD8+ (and CD4+) T cell antigens in humans. We propose that boosting H SV-2-specific CD8+ CTL in infected humans will have a therapeutic effect. Our previous STTR Phase I data show that HSV-2 tegument immunogens can be manufactured and formulated as plasmid DNA (pDNA) vaccines encoding viral proteins. The pDNA vaccines are well tolerated, elicit CD8+ T-cell responses in mice, and are protective in a murine intravaginal lethal challenge model. We also confirm work of others that truncated gD2 pDNA vaccine is immunogenic and protective. The overall goal of this phase II STTR is to carry out non-clinical animal efficacy and safety studies in support of an IND to allow rapid translation of the vaccine to the clinic. This Phase II proposal, as per NIH policy, starts six or less submission dates after Phase I. We propose the fol lowing Specific Aims: Aim 1. Determine the optimum combination of UL46, UL47, and gD2 vaccines for elicitation of HSV-2- specific CD8+ T-cell responses. Determine dose and combinations with clinical activity in two murine models with endpoints being acut e intravaginal challenge and flank zosteriform spread. Aim 2. Determine the activity of an optimized UL46/UL47/gD2 vaccine for reduction of recurrent vaginal HSV-2 shedding in the guinea pig therapeutic model. Aim 3. Compare the immunogenicity and therap eutic efficacy of electroporation-assisted and intramuscular immunization with HSV-2 pDNA vaccines in the murine and guinea pig models. Aim 4. Based on results from Aims 1-3, plan and initiate non-clinical safety studies on a candidate pDNA HSV-2 immunoth erapeutic vaccine and file an IND with the FDA.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 100.00K | Year: 1999