Abstract: The invention provides methods for T helper-independent activation of an antigen-specific cytotoxic T lymphocyte response in an individual. The methods generally involve administering to an individual an immunostimulatory nucleic acid molecule in an amount effective to increase an antigen-specific CTL response in the individual. The invention further provides methods for increasing chemokine secretion, which can block HIV infection.

Abstract: The invention features a polynucleotide vaccine modified to enhance expression of the encoded antigen in host cells. The polynucleotide vaccine comprises an antigen-encoding nucleic acid sequence derived from a non-host species of a first phylum or first kingdom, wherein the native signal sequence of the antigen coding sequence is deleted and, optionally, replaced with a signal sequence of a polypeptide of a second phylum or a second kingdom that is functional in the host to be immunized (e.g., a viral signal sequence with a plant antigen-encoding sequence). In one embodiment, the signal sequence is a hemagglutinin A (HA) signal sequence, and the antigen is an allergen (e.g., plant allergen) or from a pathogen (e.g., a bacterium, virus or parasite). The polynucleotide vaccine of the invention provides a synergistic effect with an immunostimulatory sequence (ISS) adjuvant to not only maintain, but to enhance, the immune response to the encoded antigen.

Abstract: The invention consists of oligonucleotides which inhibit the immunostimulatory activity of ISS-ODN (immunostimulatory sequence oligodeoxynucleotides) as well as methods for their identification and use. The oligonucleotides of the invention are useful in controlling therapeutically intended ISS-ODN adjuvant activity as well as undesired ISS-ODN activity exerted by recombinant expression vectors, such as those used for gene therapy and gene immunization. The oligonucleotides of the invention also have anti-inflammatory activity useful in reducing inflammation in response to infection of a host with ISS-ODN containing microbes, in controlling autoimmune disease and in boosting host Th2 type immune responses to an antigen. The invention also encompasses pharmaecutically useful conjugates of the oligonucleotides of the invention (including conjugate partners such as antigens and antibodies).

Abstract: The present invention features methods for treatment or prevention of infection by intracellular pathogens (e.g., Mycobacterium species) by administration of an immunomodulatory nucleic acid molecule. In one embodiment, immunomodulatory nucleic acid molecule are administered in combination with another anti-pathogenic agent to provide a synergistic anti-pathogenic effect.

Abstract: The invention provides a method for ameliorating gastrointestinal inflammation, particularly chronic gastrointestinal inflammation such as inflammatory bowel disease (IBD), in a subject. In one embodiment, the method comprises administering an immunomodulatory nucleic acid to a subject suffering from or susceptible to gastrointestinal inflammation.

Abstract: The invention consists of oligonucleotides which inhibit the immunostimulatory activity of ISS-ODN (immunostimulatory sequence oligodeoxynucleotides) as well as methods for their identification and use. The oligonucleotides of the invention are useful in controlling therapeutically intended ISS-ODN adjuvant activity as well as undesired ISS-ODN activity exerted by recombinant expression vectors, such as those used for gene therapy and gene immunization. The oligonucleotides of the invention also have anti-inflammatory activity useful in reducing inflammation in response to infection of a host with ISS-ODN containing microbes, in controlling autoimmune disease and in boosting host Th2 type immune responses to an antigen. The invention also encompasses pharmaceutically useful conjugates of the oligonucleotides of the invention (including conjugate partners such as antigens and antibodies).

Abstract: This invention relates to apparatus and compositions for administering antigens and immunostimulatory peptides to a mammalian host by the introduction of one or more naked polynucleotides to operatively encode for the antigens and immunostimulatory peptides, preferably by non-invasive means.

Abstract: The invention is directed to a method for treating both the early and late phases of allergic asthma by introducing naked polynucleotides which operatively encode for the asthma-initiating antigen into the host. The antigen-encoding polynucleotides are administered to host tissues which contain a high concentration of antigen presenting cells (e.g., skin and mucosa) relative to other host tissues. Expression of the asthma-initiating antigen encoding polynucleotides of the invention inside of antigen presenting cells (without substantial secretion therefrom) induces antigen tolerance while suppressing IgE antibody formation in the early phase of the disease, and also suppresses cytokine-mediated eosinophil accumulation in the late phase of the disease. Devices and compositions for use in the methods of the invention are also described.

Abstract: This invention relates to methods for administering antigens and immunostimulatory peptides to a mammalian host by the introduction of one or more naked polynucleotides to operatively encode for the antigens and immunostimulatory peptides, preferably by non-invasive means.

Abstract: The invention is directed to methods for introducing biologically active peptides into a host by administration of polynucleotides which operatively encode for the peptide of interest. In a preferred embodiment of the invention, a mammal is desensitized to an antigen, in particular an allergen, through administration to the mammal of polynucleotides which operatively encode the antigen. The antigen-encoding polynucleotides are administered to host tissues which have a high concentration of antigen presenting cells in them relative to other host tissues. The method is particularly useful in treating allergies because the allergen-encoding polynucleotides of the invention to induce tolerance while suppressing IgE antibody formation. Devices and compositions for use in the methods of the invention are also described.

Abstract: The invention is directed to methods for introducing biologically active peptides into a host by administration of polynucleotides which operatively encode for the peptide of interest. In a preferred embodiment of the invention, a host who has been identified as having a tumor bearing at least one tumor-associated antigen is the recipient of a polynucleotide which operatively encodes for a foreign mimic of the tumor-associated antigen or a mutation of the self-antigen. The antigen-encoding polynucleotides are administered to host tissues which have a high concentration of antigen presenting cells in them relative to other host tissues. The method is particularly useful in treating cancer through induction of antigen-specific cytotoxic T lymphocytes in the host for lysis of tumor cells bearing the antigen. Devices and compositions for use in the methods of the invention are also described.