Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination.

Development of CD8 alphabeta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes. Here we describe a DNA plasmid encoding a polyepitope or "polytope" protein, which contained multiple contiguous minimal murine CTL epitopes. Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models. CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help. The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.

[1]  A. Suhrbier,et al.  Multi‐epitope DNA vaccines , 1997, Immunology and cell biology.

[2]  I. Frazer,et al.  E7 oncoprotein of human papillomavirus type 16 expressed constitutively in the epidermis has no effect on E7-specific B- or Th-repertoires or on the immune response induced or sustained after immunization with E7 protein. , 1997, Virology.

[3]  J. Whitton,et al.  A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen , 1997, Journal of virology.

[4]  Martin A. Nowak,et al.  Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS , 1997, Nature Medicine.

[5]  Xiping Wei,et al.  Antiviral pressure exerted by HIV-l-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus , 1997, Nature Medicine.

[6]  J. Wands,et al.  Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids. , 1997, Journal of immunology.

[7]  J. Kim,et al.  In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. , 1997, Journal of immunology.

[8]  J. Ulmer,et al.  Generation of MHC class I‐restricted cytotoxic T lymphocytes by expression of a viral protein in muscle cells: antigen presentation by non‐muscle cells , 1996, Immunology.

[9]  U. Grohmann,et al.  IL-12 is both required and sufficient for initiating T cell reactivity to a class I-restricted tumor peptide (P815AB) following transfer of P815AB-pulsed dendritic cells. , 1996, Journal of immunology.

[10]  A. Lanzavecchia,et al.  Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation , 1996, The Journal of experimental medicine.

[11]  E. Raz,et al.  Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization , 1996, Science.

[12]  X. Mo,et al.  Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T cell epitopes. , 1996, Journal of immunology.

[13]  F. Oesch,et al.  Granulocyte‐macrophage‐colony‐stimulating factor enhances immune responses to melanoma‐associated peptides in vivo , 1996, International journal of cancer.

[14]  N. Baumgarth,et al.  In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue , 1996, Journal of virology.

[15]  M. Akashi,et al.  In vivo induction of cytotoxic T lymphocytes specific for a single epitope introduced into an unrelated molecule. , 1996, Journal of immunological methods.

[16]  E. Pamer,et al.  A recombinant minigene vaccine containing a nonameric cytotoxic-T-lymphocyte epitope confers limited protection against Listeria monocytogenes infection , 1996, Infection and immunity.

[17]  P. Matzinger,et al.  Long-lasting CD8 T cell memory in the absence of CD4 T cells or B cells , 1996, The Journal of experimental medicine.

[18]  Steven M. Wolinsky,et al.  Adaptive Evolution of Human Immunodeficiency Virus-Type 1 During the Natural Course of Infection , 1996, Science.

[19]  David Gray,et al.  Immunological Memory and Protective Immunity: Understanding Their Relation , 1996, Science.

[20]  J. Berzofsky,et al.  Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes. , 1996, Journal of immunology.

[21]  S. Hoffman,et al.  Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity , 1996, The Journal of experimental medicine.

[22]  M. V. von Herrath,et al.  CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge , 1996, Journal of virology.

[23]  J. Kirkwood,et al.  New treatment options for patients with melanoma: review of melanoma-derived T-cell epitope-based peptide vaccines , 1996, Melanoma research.

[24]  D J Moss,et al.  Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. P. Bucy,et al.  Differences in the degree of depletion, rate of recovery, and the preferential elimination of naive CD4+ T cells by anti-CD4 monoclonal antibody (GK1.5) in young and aged mice. , 1995, Journal of immunology.

[26]  Z. Xiang,et al.  Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines. , 1995, Immunity.

[27]  R. Ahmed,et al.  CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection , 1994, Journal of virology.

[28]  B. Murphy,et al.  Primary pulmonary cytotoxic T lymphocytes induced by immunization with a vaccinia virus recombinant expressing influenza A virus nucleoprotein peptide do not protect mice against challenge , 1994, Journal of virology.

[29]  H L Robinson,et al.  DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[30]  T. Elliott,et al.  Peptide selection by class I molecules of the major histocompatibility complex , 1993, Current Biology.

[31]  L. Kjer-Nielsen,et al.  Avidity for antigen can influence the helper dependence of CD8+ T lymphocytes. , 1993, Journal of immunology.

[32]  E. Kieff,et al.  Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development , 1992, The Journal of experimental medicine.

[33]  Eric O Long,et al.  Efficient cDNA expression vectors for stable and transient expression of HLA-DR in transfected fibroblast and lymphoid cells. , 1991, Human immunology.

[34]  A. Saul,et al.  Immune response to a synthetic peptide corresponding to an epitope of a parasitophorous vacuole membrane antigen from Plasmodium falciparum. , 1989, Journal of Immunology.

[35]  I. Hariharan,et al.  A lethal myeloproliferative syndrome in mice transplanted with bone marrow cells infected with a retrovirus expressing granulocyte‐macrophage colony stimulating factor. , 1989, The EMBO journal.

[36]  M. Bevan,et al.  Introduction of soluble protein into the class I pathway of antigen processing and presentation , 1988, Cell.

[37]  L. Brown,et al.  Genetic control and fine specificity of the immune response to a synthetic peptide of influenza virus hemagglutinin , 1988, Journal of virology.

[38]  P. Hass,et al.  Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule. , 1986, Biochemistry.

[39]  J. Vieira,et al.  The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. , 1982, Gene.

[40]  T. F. Smith,et al.  Replication and plaque assay of influenza virus in an established line of canine kidney cells. , 1968, Applied microbiology.

[41]  S. Rowland-Jones,et al.  Role of cellular immunity in protection against HIV infection. , 1997, Advances in immunology.

[42]  S. Burrows,et al.  Strategies involved in developing an effective vaccine for EBV-associated diseases. , 1996, Advances in cancer research.

[43]  R. Webster,et al.  DNA vaccines. , 1996, AIDS research and human retroviruses.

[44]  D. Fuller,et al.  Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. , 1995, Vaccine.

[45]  R. Gupta,et al.  Adjuvants for human vaccines--current status, problems and future prospects. , 1995, Vaccine.

[46]  R. Arlinghaus,et al.  Effects of influenza virus-specific cytotoxic T-lymphocyte responses induced by a synthetic nucleoprotein peptide on the survival of mice challenged with a lethal dose of virus. , 1994, Vaccine.

[47]  A. Saul,et al.  Chemical characterization of the parasitophorous vacuole membrane antigen QF 116 from Plasmodium falciparum. , 1990, Molecular and biochemical parasitology.