Gene inoculation generates immune responses against human immunodeficiency virus type 1.

Wang, Bin; Ugen, Kenneth E.; Srikantan, Vasantha; Agadjanyan, Michael G.; Dang, Kesen; Refaeli, Yosef; Sato, Alice I.; Boyer, Jean; Williams, William V.; Weiner, David B.

doi:10.1073/pnas.90.9.4156

Cited by 575 publications

(256 citation statements)

References 17 publications

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“…2 Direct DNA transfer has been successfully used for in vitro induction of both humoral and cellular immune responses to several antigens, including viruses such as influenza, hepatitis B, or HIV (human immunodeficiency virus), parasites, or tumor antigens. [3][4][5][6][7][8] Additionally, systemic effects were observed after transfer of cytokine genes. 9 It was assumed at the beginning that striated muscle is the only tissue in vitro suitable to take up and express naked DNA.…”

Section: Introductionmentioning

confidence: 99%

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

Förg

Hoegen

Dalemans³

et al. 1998

Gene Ther

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Three different vaccination sites were compared for expression vector used. The cytomegalus virus promoter efficiency of immunization with naked DNA. Using the bacdriven pCMV␤ vector was superior to the Moloney murine terial lacZ gene as a model, all three sites of the mouse leukemia virus LTR driven BAG vector. LacZ DNA immuni-(skeletal muscle, dermis of abdominal skin or of the ear zation was also compared with cell-based vaccination with pinna) could express the gene product ␤-gal but varied in lacZ-transfected tumor cells, in which case again the pinna expression time with muscle tissue showing the longest was the best site for inducing strong immune responses. expression. Expression time, however, did not correlateTumor-specific T cell responses could also be well induced with immune response intensity. The ear pinna was by far in the pinna, leading to cytotoxic T lymphocyte induction the most effective and muscle the least effective priming and protective antitumor immunity. Thus, the pinna was site for specific humoral and cytotoxic T cell-mediated found to be a privileged site for induction of antitumor immune responses. Following intra-pinna DNA inoculation, responses and for genetic immunization, an important find-␤-gal expressing cells were detectable around the injection ing of immediate practical and potential future clinical site and in the major draining lymph node. Efficiency of implications. immunization was also dependent on the promoter and

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Section: Introductionmentioning

confidence: 99%

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

Förg

Hoegen

Dalemans³

et al. 1998

Gene Ther

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“…6 While peptide, protein or glycoprotein vaccines elicit mainly antibody responses, DNA vaccines allow presentation of antigen to the immune system in several ways and have the potential of inducing strong cellular responses. DNA vaccines have been shown to stimulate all three arms of the immune system, that is, antibody, helper T, and cytotoxic T-cell (CTL) responses, 16 to produce immunity in several disease models such as influenza, 17,18 HIV-1, 19,20 and hepatitis B, 21 and to protect animals from subsequent challenge. 18 The mechanisms are considered to involve antigen presentation by both myocytes and antigen-presenting cells (APCs), as well as crosspriming between the two MHC paths.…”

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confidence: 99%

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system

et al. 2003

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Carcinoembryonic antigen (CEA, CEACAM5) is expressed on several human carcinomas including colon cancer. CEA contains signal peptides that target the protein through the endoplasmic reticulum and to the cell membrane. We constructed a plasmid DNA vaccine encoding a truncated CEA (DCEA), devoid of its signal peptides, and demonstrated that it was retained inside the cell, while full-length CEA (wtCEA) was expressed on the membrane. We hypothesized that intracellular retention of DCEA would enhance MHC class I presentation of CEA peptides, thus favoring cellular immune responses. In addition, a promiscuous T-helper epitope (Q830-L844 of tetanus toxoid) was fused to the N-terminal of the truncated CEA gene (tetDCEA). C57BL/6 mice immunized with DNA encoding wtCEA or tetDCEA developed both humoral and cellular immune responses to CEA. SCID mice transplanted with spleen cells from tetDCEA but not wtCEA-immunized C57BL/6 mice showed strong suppression of tumor growth after inoculation of human CEA-expressing colon carcinoma cells. Immune spleen cell populations depleted for either B, T or both B and T cells were active, indicating that effector cells might also reside in other populations. The present approach to manipulating antigen presentation may open new possibilities for immunotherapy against colon and other CEA-secreting carcinomas.

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“…We and others have developed a new strategy for the production of immunotherapy against infectious diseases as well as the treatment of speci®c types of cancers Davis et al, 1993;Kim et al, 1997b;Tang et al, 1992;Ulmer et al, 1993;Wang et al, 1993). This strategy is fundamentally di erent from previous vaccine approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Nucleic acid immunization induces antigen-speci®c immune responses following injection of non-replicating plasmids directly into a host target tissue (Boyer et al, 1997;Davis et al, 1993;Fynan et al, 1993;Kim et al, 1997a,b;Kim and Weiner, 1998;Lu et al, 1995;Tang et al, 1992;Ulmer et al, 1993;Wang et al, 1993). Once injected, these non-replicating transcription units drive the synthesis of speci®c foreign proteins within the inoculated host.…”

Section: Introductionmentioning

confidence: 99%

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine

et al. 1998

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Nucleic acid immunization has been investigated as immunotherapy for infectious diseases as well as for treating speci®c types of cancers. In this approach, nucleic acid expression cassettes are directly inoculated into the host, whose transfected cells become the production source of novel and possibly immunologically foreign protein. We have developed a DNA vaccine construct which encodes for PSA by cloning a cDNA for PSA into a mammalian expression vector under control of a CMV promoter. We investigated and characterized the immunogenicity of PSA DNA expression cassettes in mice. PSA-speci®c immune responses induced in vivo by immunization were characterized by enzyme-linked immunosorbent assay (ELISA), T helper proliferation cytotoxic T lymphocyte (CTL), and¯ow cytometry assays. We observed a strong and persistent antibody response against PSA for at least 180 days following immunization. In addition, a signi®cant T helper cell proliferation was observed against PSA protein. Using synthetic peptides spanning the PSA open frame, we identi®ed four dominant T helper epitopes of PSA. Furthermore, immunization with PSA plasmid induced MHC Class I CD8+ T cell-restricted cytotoxic T lymphocyte response against tumor cell targets expressing PSA. The prostate represents a very speci®c functional organ critical for reproduction but not for the health and survival of the individual. Understanding the immunogenicity of PSA DNA immunization cassettes o ers insight into the possible use of this tumorassociated antigen as a target for immunotherapy. These results demonstrate the ability of the genetic PSA to serve as a speci®c immune target capable of generating both humoral and cellular immune responses in vivo.

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Gene inoculation generates immune responses against human immunodeficiency virus type 1.

Cited by 575 publications

References 17 publications

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system

Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine

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