摘要:
Methods for delivering naked DNA vaccines to enhance immune responses, by improving transfection efficiency without safety concerns associated with live viral vectors, are described. A method may comprise administering to a mammalian subject an effective amount of a papillomavirus pseudovirion, wherein the papillomavirus pseudovirion comprises at least one papillomavirus capsid protein encapsidating a naked DNA vaccine, wherein the naked DNA vaccine comprises a first nucleic acid encoding at least one antigen, thereby enhancing the antigen specific immune response relative to administration of the naked DNA vaccine.
摘要:
Human papillomavirus (HPV) infection is the etiological factor for cervical cancer. Provided are HPV vaccines that generate a humoral immune response to prevent new infection, as well as cell-mediated immunotherapy to eliminate established infection or HPV-related disease. HPV vaccines include nucleic acid sequences encoding HPV16 early proteins E6 and E7. Additional nucleic acid sequences in the vaccines include sequences encoding calreticulin and/or the HPV16 late protein L2. Methods using these vaccines are provided that result in therapeutic effects.
摘要:
Novel nucleic acid vectors comprising sequences encoding (a) an antigen, (b) a signal peptide, and (c) a heat shock protein, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat tumors.
摘要:
Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.
摘要:
Nucleic acids encoding a chimeric or fusion polypeptide which polypeptide comprises a first domain comprising a translocation polypeptide; and a second domain comprising at least one antigenic peptide are disclosed. The preferred translocation polypeptide is a bacterial toxin translocation polypeptide, such as domain II of Pseudomonas aeruginosa exotoxin A (ETA(dII)). Such nucleic acids, expression vectors thereof, and cells expressing these vectors are used as vaccine compositions in a method for enhancing an antigen specific immune response, a method of increasing the numbers of CD8+ CTLs specific for a selected desired antigen in a subject, or a method of inhibiting the growth of a tumor in a subject.
摘要:
This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.
摘要:
This invention provides compositions and methods for inducing and enhancing immune responses, such as antigen-specific cytotoxic T lymphocyte (CTL) responses, using chimeric molecules comprising endoplasmic reticulum chaperone polypeptides and antigenic peptides. In particular, the invention provides compositions and methods for enhancing immune responses induced by polypeptides made in vivo by administered nucleic acid, such as naked DNA or expression vectors, encoding the chimeric molecules. The invention provides a method of inhibiting the growth of a tumor in an individual. The invention also provides novel self-replicating RNA virus constructs for enhancing immune responses induced by chimeric polypeptides made in vivo.
摘要:
The invention provides compositions and methods of vaccination that enhance the potency of DNA vaccines. The immunogenic composition contains a DNA encoding a carboxyterminal fragment of a heat shock protein operably linked to a second DNA encoding a MHC class I restricted antigen.
摘要:
Methods for treating or preventing hyperproliferating diseases, e.g., cancer, are described. A method may comprise administering to a subject in need thereof a therapeutically effective amount of a nucleic acid encoding an MHC class I and/or II activator and optionally a nucleic acid encoding an antigen.
摘要:
An immunotherapeutic strategy is disclosed that combines antigen-encoding DNA vaccine compositions combined with siRNA directed to pro-apoptotic genes, primarily Bak and Bax, the products of which are known to lead to apoptotic death. Gene gun delivery (particle bombardment) of siRNA specific for Bak and/or Bax to antigen-expressing DCs prolongs the lives of such DCs and lead to enhanced generation of antigen-specific CD8+ T cell-mediated immune responses in vivo. Similarly, antigen-loaded DC's transfected with siRNA targeting Bak and/or Bax serve as improved immunogens and tumor immunotherapeutic agents.