Improving Vaccine Potency Through Intercellular Spreading and Enhanced MHC Class I Presentation of Antigen

Hung, Chien-Fu; Cheng, Wen‐Fang; Chai, Chee‐Yin; Hsu, Keng-Fu; He, Liangmei; Ling, Morris; Wu, T. C.

doi:10.4049/jimmunol.166.9.5733

Cited by 131 publications

(94 citation statements)

References 30 publications

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“…The generation of pcDNA3-E7 has been described previously [5,25]. The generation of pcDNA3-CRT has also been described previously [5].…”

Section: Plasmid Dna Constructs and Preparationmentioning

confidence: 99%

“…Preparation of DNA-coated gold particles and gene gun particle-mediated DNA vaccinations were performed using a helium-driven gene gun according to a protocol described previously with some modifications [25]. Gene gun particle-mediated DNA vaccinations were performed using a Low Pressure-accelerated Gene Gun (BioWare Technologies Co. Ltd., Taipei, Taiwan).…”

Section: Dna Vaccinationmentioning

confidence: 99%

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Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

Cheng

Hung

Chen

et al. 2005

Vaccine

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Antigen-specific cancer immunotherapy and antiangiogenesis are feasible strategies for cancer therapy because they can potentially treat systemic tumors at multiple sites in the body while discriminating between neoplastic and non-neoplastic cells. We have previously developed a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus-16 E7 and have found that this vaccine generates strong E7-specific antitumor immunity and antiangiogenic effects in vaccinated mice. In this study, we characterized the domains of CRT to produce E7-specific antitumor immunity and antiangiogenic effects by generating DNA vaccines encoding each of the three domains of CRT (N, P, and C domains) linked to the HPV-16 E7 antigen. We found that C57BL/6 mice vaccinated intradermally with DNA encoding the N domain of CRT (NCRT), the P domain of CRT (PCRT), or the C domain of CRT (CCRT) linked with E7 exhibited significant increases in E7-specific CD8 + T cell precursors and impressive antitumor effects against E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. In addition, the N domain of CRT also showed antiangiogenic properties that might have contributed to the antitumor effect of NCRT/E7. Thus, the N domain of CRT can be linked to a tumor antigen in a DNA vaccine to generate both antigen-specific immunity and antiangiogenic effects for cancer therapy.

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“…The generation of pcDNA3-E7 has been described previously [5,25]. The generation of pcDNA3-CRT has also been described previously [5].…”

Section: Plasmid Dna Constructs and Preparationmentioning

confidence: 99%

Section: Dna Vaccinationmentioning

confidence: 99%

Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

Cheng

Hung

Chen

et al. 2005

Vaccine

Self Cite

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“…Such sequences, termed 'protein transduction domains' (PTDs), have been identified in the human immunodeficiency virus (HIV) tat protein, the herpes simplex virus (HSV) VP22 protein, the Drosophila melanogaster homeoproteins, and elsewhere (reviewed in Lindgren et al 9 and Prochiantz 10 ). These sequences have been successfully used as immunoadjuvants in several models, [11][12][13][14] and it has been postulated that the immune enhancement results from the improved delivery of these translocatory proteins to APCs. We have found that fusion of the HIV-1 tat PTD to an epitope enhanced its ability to stimulate CD8 þ T cells in vitro and in vivo, and improved antiviral protection when administered as a plasmid vaccine.…”

Section: Introductionmentioning

confidence: 99%

The cationic region from HIV tat enhances the cell-surface expression of epitope/MHC class I complexes

et al. 2003

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The potential of genetic immunization has been acknowledged for almost a decade, but disappointing immunogenicity in humans has delayed its introduction into the clinical arena. To try to increase the potency of genetic immunization, we and others have evaluated 'translocatory' proteins, which are thought to exit living cells by an uncharacterized pathway, and enter neighboring cells in an energy-independent manner. Several laboratories, including our own, have begun to question these remarkable properties. Our previous studies showed that the ability of an epitope to induce major histocompatibility complex (MHC) class I restricted CD8 þ T cells was, indeed, enhanced by its being attached to the proposed translocatory sequence of the HIV-1 tat protein. However, we found little evidence that the increased immunogenicity resulted from transfer of the fusion peptide between living cells, and we proposed that it resulted instead from an increased epitope/MHC expression on the surface of transfected cells. Here, we directly test this hypothesis. We show that cells cotransfected with plasmids encoding an epitope, and the relevant MHC class I allele, can stimulate epitope-specific T cells, and that attachment of the epitope to a putative translocatory sequence -which we term herein an 'integral cationic region' (ICR) -leads to a marked increase in stimulatory activity. This elevated stimulatory capacity does not result from a nonspecific increase in MHC class I expression. We use a high-affinity T-cell receptor (TcR) specific for the epitope/MHC combination to quantitate directly the cell-surface expression of the immunogenic complex, and we show that the attachment of the tat ICR to an epitope results in a substantial enhancement of its cellsurface presentation. These data suggest an alternative explanation for the immune enhancement seen with ICRs.

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“…More recently, the VP22 gene of BHV-1 has been used as a gene adjuvant to enhance the immunogenic activity and thus make the antigen easily recognized and processed by the organism immunity system, and VP22 can enhance immune responses in vivo in a variety of applications (Hung et al, 2001;Wills et al, 2001;Saha et al, 2006). In this work, VP22 was used as a gene adjuvant to study the enhancement of the SS DNA vaccine in mice.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the VP22 gene adjuvant for enhancement of DNA vaccine against somatostatin in mice

Han

Liang

Zhang

et al. 2008

Animal

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Somatostatin (SS) is a hormone that inhibits the secretion of growth hormone. Immunization against SS can promote the growth of animals. A novel SS-VP22 fused vaccine, pEGS2SS-V, was constructed from pEGS2SS plasmid with a VP22 gene fragment. Two times of immunization with pEGS2SS-V-induced anti-SS antibodies in mice. Compared with mice immunized with pEGS2SS and 0.85% saline, the growth performance of mice immunized with pEGS2SS-V was increased by 14.1% (P , 0.05) and 48.4% (P , 0.01) on the 2nd week after the first vaccination, respectively. The results indicated that the effects of the somatostatin DNA vaccine could be improved effectively by VP22 gene adjuvant.Keywords: BHV-1 VP22, somatostatin, DNA vaccine IntroductionThe circadian and pulsatile secretion of growth hormone (GH) from the anterior pituitary gland plays a crucial role in postnatal longitudinal growth and development, tissue growth, lactation, reproduction, as well as protein, lipid and carbohydrate metabolism (Ohlsson et al., 1998;Ayuk and Sheppard, 2006). The secretion of GH is down-regulated by somatostatin (SS), which is secreted by the hypothalamus (Vance et al., 1992). The SS has broad inhibitory effect on animals, especially on animal growth and immune response; thus, exhausting or immuno-neutralizing the SS level could lead to increase in GH and promote animal growth (Ohlsson et al., 1998). Therefore, as an alternative approach to direct GH injection, immunization against SS that inhibits GH secretion has been suggested as a method to promote the growth of animals by inactivating SS in the plasma.SS is a 14-peptide-hormone with a small molecular weight and a very short half-life. Synthetic SS conjugated to a carrier protein promotes the growth rates of immunized animals, including lambs, steers and chickens (Buonomo et al., 1987;Van Kessel et al., 1990). However, native SS preparation is limited in source.Chemical synthesis is inefficient for polypeptides longer than about 300 amino acids, and the synthesized proteins may not readily assume their native tertiary structure. Besides, these programs are time-consuming and relatively expensive, which limit the application of SS immunization to promote animal growth.DNA immunization represents a novel vaccine strategy (Tang et al., 1992). So far, there have been several reports on DNA vaccines encoding the SS gene that can promote the growth of immunized animals in our lab (Liang et al., 2008). However, the potency of naked DNA vaccines is limited by their inability to amplify and spread in vivo; in primates and other large animals the responses are less impressive and the quantities of DNA required may be large (Calarota et al., 1998;Macgregor et al., 1998;Wang et al., 1998). It was reported that the tegument protein VP22 of bovine herpesvirus-1 (BHV-1) could increase the immunogenicity of antigens to which it was fused (Oliveira et al., 2001;Wills et al., 2001;Hung et al., 2002). VP22 of BHV-1 is a 258 amino acid tegument protein (Liang et al., 1995) that can transport proteins to neighbor...

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Improving Vaccine Potency Through Intercellular Spreading and Enhanced MHC Class I Presentation of Antigen

Cited by 131 publications

References 30 publications

Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

The cationic region from HIV tat enhances the cell-surface expression of epitope/MHC class I complexes

Evaluation of the VP22 gene adjuvant for enhancement of DNA vaccine against somatostatin in mice

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