SBIR-STTR Award

This proposal is a unique collaboration between a small, but full capability, Biotechnology Company and a premier academic institution and laboratory to develop a novel product for clinical trials in cancer patients. The project provides for additional employment and economic growth benefits through the development plan, and has the potential to have significant economic benefit if the treatment becomes successful. This proposal describes a vaccine product aimed to provide a feasible and nontoxic way to elicit strong immunity in humans to HIV proteins, and it will provide an added arm to vaccine strategies such as recombinant viral vectors. The technology behind this product is based on our most recent understanding of immunology and vaccines. First, the product ensures for the first time that HIV envelope and gag antigens are efficiently targeted to antigen presenting dendritic cells by using recombinant antibody technology. This vaccine product uses a human monoclonal antibody, generated by the PI's, that can seek out and bind to the subject's dendritic cells expressing the molecule DEC-205. In this way, a large number of dendritic cells in lymphoid organs can present antigens to rare antigen-specific T cells and efficiently initiate the immune attack against HIV proteins. Second, the product includes a stimulus or adjuvant that results in a strong innate response, which in turn is required for the optimum immune response. This product encompasses proprietary immune activators with clinical and pre-clinical track record. Importantly, these agents have been secured for use in these products through licensing partnerships and agreements. Finally, the product has carefully selected specific HIV envelope and gag antigens. These antigens individually have documented immunogenicity in mice and monkeys, when delivered to DEC-205, and now need to be combined into a vaccine product suitable for further development in phase II in mice and monkeys.

Public Health Relevance:
Dendritic cells are critical for the initiation of immunity. This proposal will harness the capacities of dendritic cells to initiate antibody and cell-mediated immunity against HIV. In the phase I portion, we will produce an antibody that efficiently delivers two HIV proteins to dendritic cells, and we will carry out proof of concept for improved immunity by giving vaccine together with safe adjuvants or immune enhancers to humanized mice. This proposal therefore describes an innovative product that addresses the need to be able to use proteins in an effective and nontoxic way to elicit and boost immunity against HIV, offering the potential of considerable impact in our country and worldwide.

Thesaurus Terms:
7s Gamma Globulin;Aids Antigens;Aids Virus;Aids/Hiv;Aids/Hiv Problem;Atgn;Acquired Immune Deficiency Syndrome Virus;Acquired Immunodeficiency Syndrome Virus;Address;Adjuvant;Agonist;Agreement;Antibodies;Antigens;Area;Assay;Attention;B Blood Cells;B-Cells;B-Lymphocytes;Binding;Binding (Molecular Function);Bioassay;Biologic Assays;Biological Assay;Biotechnology;Bursa-Dependent Lymphocytes;Bursa-Equivalent Lymphocyte;Cancer Patient;Cell Function;Cell Line;Cell Mediated Immunology;Cell Process;Cell Physiology;Cell-Mediated Immunity;Cellline;Cellular Function;Cellular Immunity;Cellular Physiology;Cellular Process;Cellular Biology;Chimera Protein;Chimeric Proteins;Clinical;Clinical Treatment Moab;Clinical Trials;Collaborations;Country;Critical Paths;Critical Pathways;Data;Dendritic Cells;Development;Development Plans;Economics;Employment;Engineering;Enhancers;Ensure;Evaluation;Fusion Protein;Gagging;Generalized Growth;Goals;Growth;Hiv;Hiv Antigens;Hiv Envelope Glycoprotein Gp120;Hiv Envelope Protein Gp120;Hiv Env Protein Gp120;Hiv Vaccine;Hiv-Associated Antigens;Hiv/Aids;Hiv/Aids Vaccines;Hiv/Aids Problem;Hplc;Htlv-Iii;Htlv-Iii Antigens;Htlv-Iii Gp120;Htlv-Iii-Lav Antigens;High Performance Liquid Chromatography;High Pressure Liquid Chromatography;High Speed Liquid Chromatography;Hu-Mabs;Human;Human Immunodeficiency Viruses;Human T-Cell Leukemia Virus Type Iii;Human T-Cell Lymphotropic Virus Type Iii;Human T-Lymphotropic Virus Type Iii;Human T-Lymphotropic Virus Type Iii Antigens;Igg;Immune;Immune Response;Immunity;Immunization;Immunoglobulin G;Immunologic Sensitization;Immunologic Stimulation;Immunological Sensitization;Immunological Stimulation;Immunology;Immunostimulation;Innate Immunity;Institution;Lav Antigens;Lav-Htlv-Iii;Laboratories;Learning;Licensing;Lymphadenopathy-Associated Antigens;Lymphadenopathy-Associated Virus;Lymphoid;Man (Taxonomy);Mice;Mice Mammals;Modern Man;Molecular Interaction;Monkeys;Monoclonal Antibodies;Murine;Mus;Native Immunity;Natural Immunity;Non-Specific Immunity;Organ;P.I.C.L.C.;Pattern Recognition Receptor;Pharyngeal Reflex;Phase;Plant Embryos;Plant Zygotes;Poly Iclc;Polyinosinic-Polycytidylic Acid Stabilized With Polylysine And Carboxymethylcellulose;Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose;Process;Production;Proteins;Receptor Protein;Recombinant Antibody;Regimen;Relative;Relative (Related Person);Research;Research Activity;Retroviral Antigen Gag Protein;Secure;Seeds;Stabilized Polyriboinosinic/Polyribocytidylic Acid;Stimulus;Strains Cell Lines;Subcellular Process;Sum;T-Cells;T-Lymphocyte;Technology;Thymus-Dependent Lymphocytes;Time;Tissue Growth;Transgenic Mice;Vaccines;Veiled Cells;Viral Gag Proteins;Virus-Hiv;Arm;Base;Cell Biology;Clinical Investigation;Cultured Cell Line;Developmental;Gag Antigens;Gag Gene Products;Gag Polyproteins;Gag Protein;Gene Product;Gp120;Gp120 Env Glycoprotein;Gp120(Hiv);Group Specific Antigen;Host Response;Human Immunodeficiency Virus Vaccine;Human Monoclonal Antibodies;Immunogen;Immunogenicity;Immunoresponse;Improved;Innovate;Innovation;Innovative;Manufacturing Process;Monomer;Non-Human Primate;Nonhuman Primate;Novel;Ontogeny;Pre-Clinical;Preclinical;Prevent;Preventing;Product Development;Prophylactic;Receptor;Recombinant Viral Vector;Response;Safety Study;Seed;Thymus Derived Lymphocyte;Uptake

This proposal is a unique collaboration between a small, but full capability biotechnology company and a premier academic institution and laboratory to develop a novel product for clinical trials to prevent HIV infection. This proposal describes a vaccine product aimed to provide a feasible and nontoxic way to elicit strong immunity in humans to HIV proteins, and it will provide an added arm to be combined vaccine strategies such as recombinant viral vectors. The technology behind this product is based on our most recent understanding of immunology and vaccines. First, the product ensures for the first time that HIV envelope and gag antigens are efficiently targeted to antigen presenting dendritic cells by using recombinant antibody technology. This vaccine product uses a human monoclonal antibody, generated by the PI's, which can seek out and bind to the subject's dendritic cells expressing the molecule DEC-205. In this way, a large number of dendritic cells in lymphoid organs can present antigens to rare antigen-specific T cells and efficiently initiate the immune attack agains HIV proteins. Second, the product includes a stimulus or adjuvant that results in a strong innate response, which in turn is required for the optimum immune response. This product encompasses proprietary immune activator with clinical and pre-clinical track record. Finally, the product has carefully selected specific HIV envelope and gag antigens, and has demonstrated feasibility of manufacturing and proof of concept in our Phase I program. This project will now be focused on further demonstrating the value of a prime boost approach with a viral vector vaccine, and manufacturing product for human use and other studies that will support a clinical trial in healthy volunteers for assessing the potential of the vaccine to preven HIV infection.

Public Health Relevance Statement:


Public Health Relevance:
Dendritic cells are critical for the initiation of immunity. This proposal will harness the capacities of dendritic cells to initiate antibody and cell-mediated immunity against HIV. In the phase I portion, we produced an antibody that efficiently delivers two HIV proteins to dendritic cells, and showed proof of concept for improved immunity by giving vaccine together with safe adjuvants to mice. In the Phase 2 portion, we will confirm the increaded immunogenicity of a prime boost approach with a viral vector HIV vaccine and also make the product ready for clinical testing by conducting GMP manufacturing and performing the safety and animal studies to support the Investigational New Drug (IND) application. This proposal therefore describes an innovative product that addresses the need to be able to use proteins in an effective and nontoxic way to elicit and boost immunity against HIV, offering the potential of considerable impact in our country and worldwide.

Project Terms:
Address; Adjuvant; Adverse drug effect; Agreement; ALVAC; Animals; Antibodies; Antigens; arm; assay development; B-Lymphocytes; base; Binding (Molecular Function); Biological Assay; Biotechnology; CD8B1 gene; cell bank; Cellular Immunity; Clinical; Clinical Trials; Collaborations; Combined Vaccines; Commit; Consensus; Country; cross reactivity; Data; Dendritic Cells; design; Dose; Drug Packaging; Ensure; Excision; experience; Funding; gag Gene Products; Gagging; Goals; healthy volunteer; HIV; HIV Infections; HIV vaccine; Human; human monoclonal antibodies; human tissue; Immune; Immune response; Immunity; Immunization; immunogenic; immunogenicity; Immunology; improved; In Vitro; in vivo; innovation; Institution; Intramuscular; Investigational Drugs; Investigational New Drug Application; Laboratories; Lymphoid; manufacturing process; meetings; Mus; nonhuman primate; novel; Organ; Pharmaceutical Preparations; Phase; Poly ICLC; Positioning Attribute; pre-clinical; prevent; Process; product development; Production; programs; Proteins; public health relevance; Qualifying; Randomized; Recombinant Antibody; recombinant viral vector; Regimen; Relative (related person); research clinical testing; Research Design; response; Safety; safety testing; Small Business Innovation Research Grant; Source; Stimulus; T cell response; T-Lymphocyte; Technology; Testing; Time; Universities; vaccine development; vaccine evaluation; Vaccines; validation studies; vector vaccine; Viral Vector; Virus; volunteer; Work