Despite close to 40 million HIV-infected individuals worldwide and millions of new infections each year, intense research in the field of HIV vaccine development has not yet lead to a licensed prophylactic or therapeutic vaccine. Regardless of the route of infection, HIV targets mucosal cells of the gastrointestinal, respiratory and genitourinary tracts, at both early and late stages of infection. HIV transmission through the female genital tract (FGT) remains a major route of infection. Thus, generation of immune responses at this mucosal portal of HIV entry, as well as systemic sites would be advantageous. Induction of immune responses at mucosal sites requires safe and effective immune enhancing delivery systems and adjuvants, which currently do not exist in licensed form mainly due to their toxicity issues. In phase I of this proposal, we will test in mice the effectiveness of a novel and safe formulation designated mucosal immune enhancing delivery system (MIDS) for mucosal (intra-nasal) and systemic (intra-dermal) administration of an HIV-envelope protein with the goal of inducing immunity in both FGT and systemic tissues. The specific aims will include first optimization of the MIDS formulations and induction of in vitro innate responses in epithelial and antigen-presenting cells (APC), followed by in vivo induction in mice of mucosal and systemic innate and adaptive responses by antigen-presenting, B and T cells, including regulatory (Treg), helper (TH) and cytotoxic (CTL). In phase II, we will test the immunogenicity and protective efficacy of immunizations with MIDS with HIVenv proteins in female rhesus macaques followed by intra-vaginal challenge with SHIV.
Public Health Relevance: Currently, there are no licensed vaccines against infections with HIV. This project pertains to designing a novel, safe and effective Mucosal Immune-enhancing Delivery System for HIV vaccine development that can protect the public against new infections with the HIV virus.
Public Health Relevance Statement: Project Narrative SBIR Phase I, January 6, 2009 Project Title: Mucosal Immune-enhancing delivery system for HIV vaccines Principal Investigator: Michael Vajdy Ph.D. Institution: EpitoGenesis Inc., 112 La Casa Via, suite 160, Walnut Creek, CA 94598. Currently, there are no licensed vaccines against infections with HIV. This project pertains to designing a novel, safe and effective Mucosal Immune-enhancing Delivery System for HIV vaccine development that can protect the public against new infections with the HIV virus.
NIH Spending Category: Biotechnology; Immunization; Prevention; Vaccine Related
Project Terms: (+)-Cyanidanol; 2-Phenyl-Benzopyrans; 2-Phenyl-Chromenes; 2H-1-Benzopyran-3,5,7-triol, 2-(3,4-dihydroxyphenyl)-3,4-dihydro-, (2R-trans)-; 3,3',4',5,7-Flavanpentol; AIDS Virus; APC; ATGN; Acquired Immune Deficiency Syndrome Virus; Acquired Immunodeficiency Syndrome Virus; Adjuvant; Administration, Cutaneous; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Antibody Formation; Antibody Production; Antibody Response; Antigen-Presenting Cells; Antigens; Antiinflammatories; Antiinflammatory Agents; Assay; B Cell Differentiation Factor I; B blood cells; B cell growth factor 2; B-Cell Growth Factor-II; B-Cells; B-Lymphocytes; BALB/c; BCGF-II; BCGF2; BCGF2 (B cell growth factor 2); Bioassay; Biologic Assays; Biological Assay; Blood Serum; Body Tissues; Bursa-Dependent Lymphocytes; Bursa-Equivalent Lymphocyte; CSIF; CSIF-10; CTL; Catechin; Catechinic Acid; Catechuic Acid; Cell Line; Cell Lines, Strains; Cell-Mediated Lympholytic Cells; CellLine; Cells; Cervical Lymph Node; Cervical lymph node group; Cianidanol; Common iliac lymph node; Country; Cutaneous Administration; Cutaneous Drug Administration; Cytokine Synthesis Inhibitory Factor; Cytokine formation-inhibiting factor (mouse clone F115 protein moiety reduced); Cytokines, Chemotactic; Cytolytic T-Cell; Cytotoxic T Cell; Cytotoxic T-Lymphocytes; Data; Dermal; Dermal Administration; Developed Countries; Developed Nations; Developing Countries; Developing Nations; Doctor of Philosophy; Drug Administration, Dermal; Drug Formulations; EDF; ELISA; ELISPOT; Edodekin Alfa; Effectiveness; Envelope Glycoprotein gp120, HIV; Enzyme-Linked Immunosorbent Assay; Eo-CSF; Eosinophil Differentiation Factor; Epithelial; Epithelial Cells; Equilibrium; Face; Fees; Female; Flavonoids; Formulation; Formulations, Drug; Gamma Globulin, 19S; Gamma Globulin, 7S; Generations; Genital; Genital System, Female, Vagina; Genital system; Genitourinary; Genitourinary system; Goals; HIV; HIV Envelope Protein gp120; HIV Infections; HIV envelope protein; HIV vaccine; HIV-1; HIV-I; HIV/AIDS Vaccines; HIV1; HTLV-III; HTLV-III Infections; HTLV-III gp120; HTLV-III-LAV Infections; Homologous Chemotactic Cytokines; Hour; 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 immunodeficiency virus 1; Human, General; IL-10; IL-12; IL-5; IL10; IL10A; IL12; IL5; IgA; IgA enhancing factor; IgG; IgG1; IgM; Iliac Lymph Node; Immune; Immune response; Immunity; Immunization; Immunodeficiency Virus Type 1, Human; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Accessory Cells; Immunologic Stimulation; Immunological Stimulation; Immunostimulation; Immunosuppressants; Immunosuppressive Agents; In Vitro; Inbred BALB C Mice; Individual; Industrialized Countries; Industrialized Nations; Infection; Inflammatory; Institution; Intercrines; Interleukin 10 Precursor; Interleukin 5 (Colony-Stimulating Factor, Eosinophil); Interleukin 5 Precursor; Interleukin-10; Interleukin-12; Interleukin-5; Juglans; Knowledge; LAV-HTLV-III; Lead; Less-Developed Countries; Less-Developed Nations; Licensing; Lymphadenopathy-Associated Virus; Macaca mulatta; Mammals, Mice; Man (Taxonomy); Man, Modern; Marketing; Measurement; Measures; Memory; Mice; Mice, Inbred BALB C; Monocytes / Macrophages / APC; Mouse, BALB C; Mucosa; Mucosal Tissue; Mucous Membrane; Murine; Mus; NKSF; Nasal; Natural Killer Cell Stimulatory Factor; Nose; Nose, Nasal Passages; Pb element; Ph.D.; PhD; Phase; Principal Investigator; Production; Proteins; Research; Respiratory System, Nose, Nasal Passages; Reticuloendothelial System, Spleen; Rhesus; Rhesus Macaque; Rhesus Monkey; Route; SBIR; SBIRS (R43/44); SHIV; SIS cytokines; Sensitization, Immunologic; Sensitization, Immunological; Series; Serum; Site; Skin Drug Administration; Small Business Innovation Research; Small Business Innovation Research Grant; Societies; Spleen; Staging; Suspension substance; Suspensions; System; System, LOINC Axis 4; T cell replacing factor; T-Cell Replacing Factor; T-Cells; T-Lymphocyte; T-Lymphocytes, Cytotoxic; T-Lymphotropic Virus Type III Infections, Human; Technology; Testing; Thailand; Third-World Countries; Third-World Nations; Thymus-Dependent Lymphocytes; Time; TimeLine; Tissues; Toxic effect; Toxicities; Translating; Translatings; Transmission; Uganda; Under-Developed Countries; Under-Developed Nations; Urogenital; Urogenital System; Vaccinated; Vaccination; Vaccines; Vagina; Vaginal; Virus-HIV; Vitamin A; Walnut; accessory cell; antibody biosynthesis; balance; balance function; base; chemoattractant cytokine; chemokine; cultured cell line; cytokine; cytotoxic; design; designing; env Protein gp120, HIV; enzyme linked immunospot assay; facial; gastrointestinal; gene product; gp120; gp120 ENV Glycoprotein; gp120(HIV); heavy metal Pb; heavy metal lead; host response; human T cell leukemia virus III; human T lymphotropic virus III; human immunodeficiency virus vaccine; immunogen; immunogenicity; immunoglobulin biosynthesis; immunoresponse; immunosuppressive; in vivo; language translation; macrophage; mucosal site; mustard oil; neutralizing antibody; novel; prophylactic; protective efficacy; public health relevance; respiratory; response; retinol; simian HIV; simian human immunodeficiency virus; suspension; therapeutic vaccine; thymus derived lymphocyte; transmission process; urogenital system (genital part); urogenital system (urinary part); vaccine delivery; vaccine development
