Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array, and in particular a RANKL protein, RANKL fragment or RANKL peptide-VLP-array. More specifically, the invention provides a composition comprising a virus-like particle and at least one RANKL protein, RANKL fragment or RANKL peptide bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of bone diseases and as a pharmaccine to prevent or cure bone diseases and to efficiently induce immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

Abstract: The invention provides compositions and processes for the production of ordered and repetitive antigen or antigenic determinant arrays. The compositions of the invention are useful for the production of vaccines for the prevention of infectious diseases, the treatment of allergies and the treatment of cancers. Various embodiments of the invention provide for a core particle that is coated with any desired antigen in a highly ordered and repetitive fashion as the result of specific interactions.

Abstract: The present invention provides conjugates of peptide derivatives of the mammalian peptide hormones angiotensinogen, angiotensin I and angiotensin II, presented in a repetitive scaffold by coupling the peptide derivatives to a carrier, particularly a virus-like particle (VLP). The invention also provides methods of producing such conjugates, and immunotherapeutic uses of the resulting immunogen conjugates for the therapy and prophylaxis of conditions associated with the renin-activated angiotensin system.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a modified virus-like particle (VLP) comprising a VLP which can be loaded with immunostimulatory substances, in particular with DNA oligonucleotides containing non-methylated C and G (CpGs), and particular HIV peptides linked thereto. Such CpG-VLPs are dramatically more immunogenic that their CpG-free counterparts and induce enhanced B and T cell responses. The immune response against HIV peptides optionally coupled, fused or attached otherwise to the VLPs is similarly enhanced as the immune response against HIV peptides are especially directed to the Th1 type. Antigens attached to CpG-loaded VLPs may therefore be ideal vaccines for prophylactic or therapeutic vaccination against allergies, tumors and other self-molecules and chronic viral diseases.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a modified virus-like particle (VLP) comprising a VLP which can be loaded with immunostimulatory substances, in particular with DNA oligonucleotides containing non-methylated C and G (CpGs), and particular peptides derived from MelanA linked thereto. Such CpGVLPs are dramatically more immunogenic than their CpG-free counterparts and induce enhanced B and T cell responses. The immune response against MelanA peptide analogues optionally coupled, fused or attached otherwise to the VLPs is similarly enhanced as the immune response against the VLP itself. In addition, the T cell responses against the MelanA peptide analogues are especially directed to the Thl type. Antigens attached to CpG-loaded VLPs may therefore be ideal vaccines for prophylactic or therapeutic vaccination against allergies, tumors and other self-molecules and chronic viral diseases.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array, and in particular an array comprising a protein or peptide of IL-5, IL-13 or eotaxin. More specifically, the invention provides a composition comprising a virus-like particle and at least one protein, or peptide of IL-5, IL-13 and/or eotaxin bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of allergic diseases with an eosinophilic component and as a pharmaccine to prevent or cure allergic diseases with an eosinophilic component and to efficiently induce immune responses, in particular antibody responses.

Abstract: Liposomes are known to enhance the activity of K- (B-) type CpGs which trigger the production of IL-12. In the present invention, the surprising finding was made that liposomes also enhance the activity of D- (A-) type CpGs, leading to the production of IFN? in vivo. These findings are relevant for the humans situation, since IFN? rather than IL-12 is the key cytokine for the induction of Th1 responses and anti-viral protection in humans.

Abstract: The present invention is in the fields of medicine, public health, immunology, molecular biology and virology. The present invention provides, inter alia, a composition comprising a virus-like particle (VLP) and at least one antigen, wherein said antigen is a GIP protein or a GIP fragment linked to the VLP respectively. The invention also provides a method for producing the aforesaid composition. The compositions of this invention are useful in the production of vaccines, in particular, for the prevention and/or treatment of obesity and hereby, in particular, by inducing efficient immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context. Accordingly, the invention further provides for methods of treating and/or preventing obesity and other conditions.

Abstract: The present invention provides novel expression vectors which permit tight regulation of gene expression in eucaryotic cells. More specifically, the invention provides DNA vectors comprising nucleotide sequences that are transcribed to form RNA molecules which are then replicated by a temperature-sensitive replicase to form additional RNA molecules. The RNA molecules produced by replication contain a nucleotide sequence which may be translated to produce a protein of interest or which encode one or more untranslated RNA molecules. Also provided are methods for producing heterologous proteins and untranslated RNA molecules. Further provided are methods for administering heterologous proteins and untranslated RNA molecules to individuals. In addition, pharmaceutical compositions are provided comprising the DNA and RNA molecules of the invention and a pharmaceutically acceptable carrier.

Abstract: The present invention provides compositions comprising a conjugate of a hapten with a carrier in an ordered and repetitive array, and methods of making such compositions. The conjugates and compositions of the invention may comprise a variety of haptens, including hormones, toxins and drugs, especially drugs of addiction such as nicotine. Compositions and conjugates of the invention are useful for inducing immune responses against haptens, which can use useful in a variety of therapeutic, prophylactic and diagnostic regimens. In certain embodiments, immune responses generated using the conjugates, compositions and methods of the present invention are useful to prevent or treat addiction to drugs of abuse and the resultant diseases associated with drug addiction.

Abstract: The invention provides compositions and processes for the production of ordered and repetitive antigen or antigenic determinant arrays. The compositions of the invention are useful for the production of vaccines for the prevention of infectious diseases, the treatment of allergies and the treatment of cancers. Various embodiments of the invention provide for a core particle that is coated with any desired antigen in a highly ordered and repetitive fashion as the result of specific interactions.

Abstract: The present invention provides ordered and repetitive antigen arrays comprising, inter alia, compositions comprising a virus-like particle (VLP) to which is linked at least one antigen, wherein said antigen is grehlin or peptides or fragments thereof. The invention also provides methods for producing the aforesaid compositions. The compositions and methods of the invention are useful in the production of vaccines and to efficiently induce self-specific immune responses, in particular antibody responses. The invention also provides for compositions and methods for the prevention and/or treatment of ghrelin-related conditions, disorders or diseases. For example, the compositions of the invention are useful in the production of vaccines for the prevention or treatment of obesity and other disease associated with increased food-uptake or increased body weight.

Abstract: The present invention provides compositions comprising a conjugate of a hapten with a carrier in an ordered and repetitive array, and methods of making such compositions. The conjugates and compositions of the invention may comprise a variety of haptens, including hormones, toxins and drugs, especially drugs of addiction such as nicotine. Compositions and conjugates of the invention are useful for inducing immune responses against haptens, which can use useful in a variety of therapeutic, prophylactic and diagnostic regimens. In certain embodiments, immune responses generated using the conjugates, compositions and methods of the present invention are useful to prevent or treat addiction to drugs of abuse and the resultant diseases associated with drug addiction.

Abstract: The present invention relates to nucleic acids encoding novel polypeptides that modulate immune responses as well as corresponding recombinant vectors and host cells comprising said vectors. The invention also encompasses the above mentioned polypeptides, derivatives thereof, antibodies directed against said polypeptides and corresponding hybridoma cell lines. Furthermore, the invention is directed at pharmaceutical compositions comprising the above mentioned nucleic acids, vectors, polypeptides and/or antibodies. In addition, the present invention is directed to a method of identifying a compound that modulates a cell response, and a method of treating and/or preventing a disease in a mammal, wherein said disease benefits from an enhanced or reduced immune response. A further aspect provides a method of producing a polypeptide, nucleic acid, vector or antibody according to the invention.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array, and in particular an A&bgr;1-6 peptide-VLP-composition. More specifically, the invention provides a composition comprising a virus-like particle and at least one A&bgr;1-6 peptide bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of Alzheimer's disease and as a pharmaccine to prevent or cure Alzheimer's disease and to efficiently induce immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

Abstract: The invention relates to the finding that virus like particles (VLPs) can be loaded and packaged, respectively, with DNA oligonucleotides rich in non-methylated C and G (CpGs). If such CpG-VLPs are mixed with antigens, the immunogenicity of these antigens are dramatically enhanced. In addition, the T cell responses against the antigens are especially directed to the Th1 type. Surprisingly, no covalent linkage of the antigen to the VLP is required; it is sufficient to simply mix the VLPs with the adjuvants for co-administration. In addition, it was found that VLPs did not enhance immune responses unless they were loaded and packaged, respectively, with CpGs. Antigens mixed with CpG-packaged VLPs may therefore be ideal vaccines for prophylactic or therapeutic vaccination against allergies, tumors and other self-molecules and chronic viral diseases.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array, and in particular a prion peptide or prion protein-VLP-array. More specifically, the invention provides a composition comprising a virus-like particle and at least one prion protein (PrP) or a dimer thereof, or a PrP peptide bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of prion diseases and as a pharmaccine to prevent or cure prion diseases and to efficiently induce immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array. The invention also provides a process for producing an antigen or antigenic determinant in an ordered and repetitive array. The ordered and repetitive antigen or antigenic determinant is useful in the production of vaccines for the treatment of infectious diseases, the treatment of allergies and as a pharmaccine to prevent or cure cancer and to efficiently induce self-specific immune responses, in particular antibody responses.

Abstract: The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array. The invention also provides a process for producing an antigen or antigenic determinant in an ordered and repetitive array. The ordered and repetitive antigen or antigenic determinant is useful in the production of vaccines for the treatment of infectious diseases, the treatment of allergies and as a pharmaccine to prevent or cure cancer and to efficiently induce self-specific immune responses, in particular antibody responses.

Abstract: The present invention relates to methods for the modification of genomes of eukaryotic cells to alter the expression of endogenous genes. The invention also relates to recombinant eukaryotic host cells and polypeptides produced by the practice of the disclosed methods. The invention further relates to vector systems useful for modifying the genomes of eukaryotic cells to alter the expression of endogenous genes.