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 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.
Jay A. Berzofsky - Bethesda MD C. David Pendleton - Bethesda MD Stephen M. Feinstone - Washington DC Marian E. Major - Alexandria VA Pablo Sarobe - Pamplona, ES
Assignee:
The United States of America as represented by the Department of Health and Human Services - Washington DC
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 LâA 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.
Jay A. Berzofsky - Bethesda MD Igor M. Belyakov - Gaithersburg MD Michael A. Derby - Germantown MD Brian L. Kelsall - Washington DC Warren Strober - Bethesda MD
Assignee:
The United States of America, as represented by the Department of Health and Human Services - Washington DC
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.
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.
Peptides Which Elicit A High Neutralizing Antibody Titer, Cytotoxic T Lymphocyte Response And T Helper Cell Response In A Broad Range Of Mhc Type Recipients
Jay A. Berzofsky - Bethesda MD, US Jeffrey D. Ahlers - Kensington MD, US C. David Pendleton - Bethesda MD, US Peter Nara - Frederick MD, US Mutsunori Shirai - Kagawa, JP
Assignee:
The United States of America as represented by the Secretary of the Department of Health and Human Services - Washington DC
International Classification:
A61K 39/21
US Classification:
4241881, 4242081, 4241921, 530324, 530325, 530326
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. Spleen cells from mice of three distinct MHC haplotypes sharing the Dclass I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.
Targeting Antigens To The Mhc Class I Processing Pathway With An Anthrax Toxin Fusion Protein
Kurt Klimpel - San Diego CA, US Theresa J. Goletz - Kensington MD, US Naveen Arora - Delhi, IN Stephen H. Leppla - Bethesda MD, US Jay A. Berzofsky - Bethesda MD, US
Assignee:
The United States of America as represented by the Department of Health and Human Services - Washington DC
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.
Samir N. Khleif - Silver Spring MD, US Jay A. Berzofsky - Bethesda MD, US
Assignee:
The United States of America as represented by the Department of Health and Human Services - Washington DC
International Classification:
C12Q 1/68
US Classification:
435 6, 435 691, 435325
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.
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.