Abstract: Methods are provided herein to prevent a tumor recurrence in a subject, involving administering to the subject an agent that blocks the TGF-? signaling pathway. In one embodiment, the agent inhibits the immunosuppressive effects of TGF-?. Also provided is a method of enhancing an immune respond in a subject to inhibit recurrence of a tumor by administering an agent which blocks the TGF-? signaling pathway. A method of enhancing the activity of an immune cell to inhibit recurrence of a tumor by contacting a TGF-? receptor-expressing cell with an agent which blocks the TGF-? signaling pathway is also provided, as are methods of screening for an agent that inhibits or measurably reduces the recurrence of a tumor.

Abstract: The invention provides methods for induction of an antigen-specific, mucosal cytotoxic T lymphocyte response useful in preventing and treating infections with pathogens that gain entry via a mucosal surface.

Abstract: Provided are an isolated peptide having the amino acid sequence DLMGYIPAV (SEQ ID NO: 1), an isolated HCV core polypeptide comprising an L?A substitution at amino acid position 139, an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2, and a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence of SEQ ID NO:1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. Further provided are methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

Abstract: The invention provides methods for induction of an antigen-specific, mucosal cytotoxic T lymphocyte response useful in preventing and treating infections with pathogens that gain entry via a mucosal surface.

Abstract: This invention provides immunogenic peptides from the HPV-18E6 protein that comprise class I restricted T cell epitopes and discloses methods of administering these peptides to individuals, and a method for monitoring or evaluating an immune response to HPV with these peptides.

Abstract: The present invention provides 1) an isolated peptide having the amino acid sequence DLMGYIPAV, (SEQ ID NO: 1); 2) an isolated HCV core polypeptide comprising an L→A substitution at amino acid position 139; 3) an isolated HCV core polypeptide having the amino acid sequence of SEQ ID NO: 2; and 4) a fragment of an HCV core polypeptide having fewer amino acids than the entire HCV core polypeptide and comprising the amino acid sequence SEQ ID NO: 1. Also provided are nucleic acids which encode the peptides and polypeptides of this invention, vectors comprising the nucleic acids of this invention and cells comprising the vectors and nucleic acids of this invention. The present invention further provides methods of producing an immune response in a subject and/or treating or preventing HCV infection in a subject, comprising administering to the subject, or to a cell of the subject, any of the compositions of this invention.

Abstract: The present invention provides a vaccine for inducing an immune response in mammal to a specific antigen, where the vaccine comprises a unit dose of a binary toxin protective antigen and the antigen, which is bound to a binary toxin protective antigen binding protein. In one embodiment the vaccine is comprised of an anthrax protective antigen and the antigen bound to anthrax protective antigen binding protein. The present invention also provides a method of immunizing a mammal against an antigen using the vaccine, and a method of inducing antigen-presenting mammalian cells to present specific antigens via the MHC class I processing pathway.

Abstract: The present invention provides a vaccine for inducing an immune response in mammal to a specific antigen, where the vaccine comprises a unit dose of a binary, cytotoxic T lymphocyte vaccine comprising an anthrax protective antigen and a full length protein antigen bound to a nontoxic anthrax protective antigen binding protein comprising at least about the first 250 amino acid residues of the lethal factor of Bacillus anthracis and less than all of the amino acid residues of the lethal factor. The present invention also provides a method of immunizing a mammal against an antigen using the vaccine, and a method of inducing antigen-presenting mammalian cells to present specific antigens via the MHC class I processing pathway.

Abstract: Improved methods for designing molecular conjugate therapeutics are described. Antibodies are described having specificity for a targeting antigen, said antigen comprising one or more MHC-binding peptides bound to a corresponding class I MHC molecule. When linked to a label or toxic agent, the resulting antibody conjugate can be used for diagnosis, imaging and for treatment against pathogens.

Abstract: A novel method of immunization, which can be used either prophylactically or therapeutically, is described. The method comprises coating of antigen presenting cells with a peptide and administering the peptide-coated cells to a mammalian subject to provoke an immune response. Useful peptides include peptides derived from viral or bacterial antigens or mutant oncogene or tumor suppressor gene products. Immunogens, constituted by the peptide-coated cells, are also described.

Abstract: A novel method of immunization, which can be used either prophylactically or therapeutically, is described. The method comprises coating of antigen presenting cells with a peptide and administering the peptide-coated cells to a mammalian subject to provoke an immune response. Useful peptides include peptides derived from viral or bacterial antigens or mutant oncogene or tumor suppressor gene products. Immunogens, constituted by the peptide-coated cells, are also described.

Abstract: The present invention provides a vaccine for inducing an immune response in mammal to a specific antigen, where the vaccine comprises a unit dose of a binary toxin protective antigen and the antigen, which is bound to a binary toxin protective antigen binding protein. In one embodiment the vaccine is comprised of an anthrax protective antigen and the antigen bound to anthrax protective antigen binding protein. The present invention also provides a method of immunizing a mammal against an antigen using the vaccine, and a method of inducing antigen-presenting mammalian cells to present specific antigens via the MHC class I processing pathway.

Abstract: Method for eliciting an immune response in a vertebrate subject are provided involving administration of a peptide antigen to the subject in a coordinated vaccination procedure that also involves administration of a non-viral vector that encodes a T cell co-stimulatory molecule. The peptide antigen contains at least one T cell epitope and may include an epitope of a tumor antigen or an antigen of a viral or non-viral pathogen. Epitopes from tumor antigens may represent fragments or partial amino acid sequences of p53, ras, rb, mcc, apc, dcc; nfl; VHL; MEN1, MEN2, MLM, Her-2neu, CEA, PSA; Muc1, Gp100, tyrosinase, or MART1 proteins, and often span a mutation identified in the tumor antigen. Various viral antigens may be selected, for example antigens identified in a human immunodeficiency virus (HIV), hepatitis B virus (HBV), herpes simplex virus (HSV) or human papilloma virus (HPV), for production of peptide antigens corresponding to immunogenic epitopes of the viral antigen.

Abstract: Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73% of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90% neutralization in the range of 1:1000 to 1:16,000 were achieved.

Abstract: The invention is directed to peptides of the HIV-1 envelope protein presenting multiple immune determinants. The peptide elicits both humoral and cell-mediated immune responses in mice having a variety of MHC types. In other embodiments, the invention is directed to immunogens composed of the peptides and methods for immunization employing them.

Abstract: A method of immunizing a mammal against a tumor cell by exposing splenic or peripheral blood mononuclear cells to a peptide that encompasses a fusion joint of a fusion protein encoded by DNA spanning a human chromosomal translocation associated with Ewing's sarcoma (t(11;22)(q24;q12)) or alveolar rhabdomyosarcoma (t(2:13)(q35;q14)) is provided.

Abstract: The cytotoxic T cell response to the protein encoded by the NS5 region of hepatitis C virus was determined using 28 peptides from NS5 which were selected by an amphipathicity algorithm as candidates for T cell epitopes. In BALB/c mice, a single relatively conserved epitope represented by a 16-residue synthetic peptide was presented by D.sup.d class I major histocompatibility complex (MHC) molecules to conventional CD4.sup.- CD8.sup.+ CTL. An exemplary peptide, which represents amino acid residues 2422-2437 of the polyprotein of the Chiron HCV1 isolate, had the amino acid sequence MSYSWTGALVTPCAAE [SEQ ID NO: 1]. A CTL line specific for this peptide recognized the two known natural variants of this NS5 sequence, each with conservative substitutions. Thus, CTL can recognize the product of the HCV NS5 gene, the probable RNA polymerase, in association with class I MHC molecules on model target cells and may recognize the same epitope on hepatocytes or any other cells infected with the virus.

Abstract: Peptides having high activity in the eliciting of a cytotoxic T lymphocyte response to the HIV-1 envelope glycoprotein gpl60 are described. The activation of 12-15 residue peptides by proteolytic degradation to shorter peptides is shown as are general techniques for characterizing such activation processes.

Abstract: This invention relates to the selection and preparation of synthetic peptides which stimulate helper T lymphocyte response to HIV in a wide range of human subjects. These multideterminant peptides are, therefore, useful for the production of vaccines against HIV infection and for diagnostic procedures to test for HIV seroconversion.

Abstract: This invention is directed toward a multideterminant human immunodeficiency virus type 1 (HIV-1) peptide which comprises a covalently linked T-helper (Th) lymphocyte epitope, cytotoxic T-lymphocyte (CTL) epitope, and an epitope capable of eliciting a neutralizing antibody response (AbN), wherein said peptide has the following amino acid sequence: KQIINMWQEVGKAMYAPPISGQIRRIHIGPGRAFYTTKN. This peptide has the further characteristic of evoking all three of these immune responses in hosts having a broad range of major histocompatibility complex (MHC) types. This peptide is useful as an immunogen to generate broad immune responses in a host, to assess immune responses in virally infected hosts, and as a diagnostic reagent to detect viral infection.