Abstract: Immunostimulatory polynucleotide-immunomodulatory molecule conjugate compositions are disclosed, These compositions include a polynucleotide that is linked to an immunomodulatory molecule, which molecule comprises an antigen and may further comprise immunomodulators such as cytokines and adjuvants. The polynucleotide portion of the conjugate includes at least one immunostimulatory oligonucleotide nucleotide sequence (ISS). Methods of modulating an immune response upon administration of the polynucleotide-immunomodulatory conjugate preparation to a vertebrate host are also disclosed.

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 consists of recombinant gene expression vectors and vaccines useful in immunization of a host against an antigen and methods for use of such vectors and vaccines. In particular, the recombinant gene expression vectors of the invention are plasmids, cosmids or viruses which include non-coding, palindromic regions of single or double-stranded DNA or RNA polynucleotides which include at least one cytosine-guanine dinucleotide motif in each palindrome. These polynucleotide regions of each expression vector are immunostimulatory and serve as adjuvants to vaccination protocols against target antigens. Most preferably, the recombinant gene expression vectors of the invention are naked; i.e., non-viral vectors not associated with a delivery vehicle such as a liposome. The invention also includes live viral vaccines wherein the viruses include immunostimulatory polynucleotides of the invention.

Abstract: The invention consists of recombinant gene expression vectors and vaccines useful in immunization of a host against an antigen and methods for use of such vectors and vaccines. In particular, the recombinant gene expression vectors of the invention are plasmids, cosmids or viruses which include non-coding, palindromic regions of single or double-stranded DNA or RNA polynucleotides which include at least one cytosine-guanine dinucleotide motif in each palindrome. These polynucleotide regions of each expression vector are immunostimulatory and serve as adjuvants to vaccination protocols against target antigens. Most preferably, the recombinant gene expression vectors of the invention are naked; i.e., non-viral vectors not associated with a delivery vehicle such as a liposome. The invention also includes live viral vaccines wherein the viruses include immunostimulatory polynucleotides of the invention.

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 present invention provides methods for modulating cell death in a eukaryotic cell, and methods for reducing DNA damage in a eukaryotic cell. The methods generally comprise modulating a biological activity of DNA-PK in a cell. The invention further provides methods of treating a condition related to cell death in an individual. The invention further provides methods of identifying agents which modulate a biological activity of DNA-PK, as well as agents identified by the methods. Methods of modulating an immune response using an identified agent are also provided.

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: Immunostimulatory polynucleotide-immunomodulatory molecule conjugate compositions are disclosed. These compositions include a polynucleotide that is linked to an immunomodulatory molecule, which molecule comprises an antigen and may further comprise immunomodulators such as cytokines and adjuvants. The polynucleotide portion of the conjugate includes at least one immunostimulatory oligonucleotide nucleotide sequence (ISS). Methods of modulating an immune response upon administration of the polynucleotide-immunomodulatory conjugate preparation to a vertebrate host are also disclosed.

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 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 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 relates to immunostimulatory oligonucleotide compositions. These oligonucleotides comprise an immunostimulatory octanucleotide sequence. These oligonucleotides can be administered in conjunction with an immunostimulatory peptide or antigen. Methods for modulating an immune response upon administration of the oligonucleotide are also disclosed. In addition, an in vitro screening method to identify oligonucleotides with immunostimulatory activity is provided.

Abstract: The present invention provides methods for modulating cell death in a eukaryotic cell, and methods for reducing DNA damage in a eukaryotic cell. The methods generally comprise modulating a biological activity of DNA-PK in a cell. The invention further provides methods of treating a condition related to cell death in an individual. The invention further provides methods of identifying agents which modulate a biological activity of DNA-PK, as well as agents identified by the methods. Methods of modulating an immune response using an identified agent are also provided.

Abstract: The invention consists of recombinant gene expression vectors and vaccines useful in immunization of a host against an antigen and methods for use of such vectors and vaccines. In particular, the recombinant gene expression vectors of the invention are plasmids, cosmids or viruses which include non-coding, palindromic regions of single or double-stranded DNA or RNA polynucleotides which include at least one cytosine-guanine dinucleotide motif in each palindrome. These polynucleotide regions of each expression vector are immunostimulatory and serve as adjuvants to vaccination protocols against target antigens. Most preferably, the recombinant gene expression vectors of the invention are naked; i.e., non-viral vectors not associated with a delivery vehicle such as a liposome. The invention also includes live viral vaccines wherein the viruses include immunostimulatory polynucleotides of the invention.

Abstract: The invention relates to methods for preventing or reducing antigen-stimulated, granulocytemediated inflammation in tissue of an antigen-sensitized mammal host by delivering an immunostimulatory oligonucleotide to the host. In addition, methods for using the immunostimulatory oligonucleotides to boost a mammal host's immune responsiveness to a sensitizing antigen (without immunization of the host by the antigen) and shifting the host's immune responsiveness to a Th1 phenotype to achieve various therapeutic ends are provided. Kits for practicing the methods of the invention are also provided.

Abstract: The present invention provides methods of maintaining suppression of a Th2 immune response, and methods of maintaining an increase in a Th1 immune response in an individual. The methods generally involve administering to an individual an effective amount of a first dose of a composition comprising an immunomodulatory nucleic acid, and, after a suitable time, administering at least a second dose of a composition comprising an immunomodulatory nucleic acid.

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 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 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: The invention relates to methods for preventing or reducing antigen-stimulated, granulocyte-mediated inflammation in tissue of an antigen-sensitized mammal host by delivering an immunostimulatory oligonucleotide to the host. In addition, methods for using the immunostimulatory oligonucleotides to boost a mammal host's immune responsiveness to a sensitizing antigen (without immunization of the host by the antigen) and shifting the host's immune responsiveness to a Th1 phenotype to achieve various therapeutic ends are provided. Kits for practicing the methods of the invention are also provided.