Helper T cell determinant peptide contributes to induction of cellular immune responses by peptide vaccines against hepatitis C virus.

Hiranuma, Kiyohiko; Tamaki, Shigenori; Nishimura, Yuki; Kusuki, Shigenori; Isogawa, Masanori; Kim, Gisen; Kaito, Masahiko; Kuribayashi, Kagemasa; Adachi, Yukihiko; Yasutomi, Yasuhiro

doi:10.1099/0022-1317-80-1-187

Cited by 36 publications

(29 citation statements)

References 43 publications

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“…14,15 In addition to those artificial polyepitope vaccines, naturally linked and usually overlapping CTL and T h epitopes also performed well as vaccines in preclinical mouse models. 16,17 Furthermore, naturally occurring, linked CTL and T h epitopes with improved immunogenicity are present in humans, such as human papillomavirus (HPV), 18,19 NY-ESO-1 (a cancer testis antigen), 20 and HER-2/neu.…”

Section: Therapeutic Vaccines Combined With Chemotherapymentioning

confidence: 99%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.

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Section: Therapeutic Vaccines Combined With Chemotherapymentioning

confidence: 99%

A new era in anticancer peptide vaccines

Perez

Hofe

Kallinteris

et al. 2010

Cancer

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“…Cytotoxic CD8 cell priming is improved by the inclusion of MHC class II (MHC II) epitopes in peptide-based vaccines (16)(17)(18)(19), showing stronger antitumor activity even toward MHC II-negative tumors (20). CD4 T cells can also display antitumor activity by themselves (14,21,22), either directly or by secreting lymphokines that recruit and activate innate effector cells: macrophages (14), NK cells (22), and eosinophils (21).…”

mentioning

confidence: 99%

Long Peptide Vaccination Can Lead to Lethality through CD4+ T Cell-Mediated Cytokine Storm

Kitamura

Sedlik

Jacquet

et al. 2010

The Journal of Immunology

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The optimization of anticancer therapeutic vaccines can lead to better efficacy but also to stronger adverse effects. In a mouse model of antitumor vaccination using a long peptide (LP), which included MHC class I- and II-restricted male (H-Y) epitopes, we observed unexpected mortality. Mice with an increased frequency of anti–H-Y CD4 T cells were primed with LP+CpG and boosted 10 d later. Within hours of boost, they displayed shock-like signs with high mortality. Serum cytokine levels were high. TNF-α secreted by the CD4 T cells was identified as the key effector molecule. Priming with a short peptide (SP), which included the MHC class II-restricted epitope, was a more efficient primer than LP, but did not lead to mortality when used as boost. The high mortality induced by LP compared with SP was probably related to its specific ability to be presented by B cells. Finally, targeting the LP sequence to dendritic cells allowed tumor protection without side effects. Our data: 1) confirm that the immune system can be very dangerous; 2) caution against the use of systemic activation of high-frequency Ag-specific T cells as induced by high doses of LP; and 3) underline the benefit of targeting Ag to dendritic cells.

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“…Although such models may prove suitable for testing antiviral compounds, they will probably be of little use for immunological and vaccination studies. The protective efficacy of any experimental vaccine formulation can best be assessed in an in vivo bioassay model, and to date both stably transfected cell lines and recombinant vaccinia virus expressing HCV antigens have been used to simulate a challenge with HCV (16,23,44,45). Since L. monocytogenes exhibits a hepatotropic intracellular phenotype, we propose that recombinant L. monocytogenes expressing HCV antigens provides another useful challenge model for the evaluation of HCV-specific CTL responses.…”

Section: Discussionmentioning

confidence: 99%

DNA Vaccination Protects Mice against Challenge withListeria monocytogenesExpressing the Hepatitis C Virus NS3 Protein

et al. 2003

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The goal of this study was to develop a new surrogate challenge model for use in evaluating protective cell-mediated immune responses against hepatitis C virus (HCV) antigens. The use of recombinant Listeria monocytogenes organisms which express HCV antigens provides novel tools with which to assay such in vivo protection, as expression of immunity against this hepatotropic bacterial pathogen is dependent on antigenspecific CD8 ؉ T lymphocytes. A plasmid DNA vaccine encoding a ubiquitin-NS3 fusion protein was generated, and its efficacy was confirmed by in vivo induction of NS3-specific, gamma interferon-secreting T cells following vaccination of BALB/c mice. These immunized mice also exhibited specific in vivo protection against subsequent challenge with a recombinant L. monocytogenes strain (TC-LNS3) expressing the NS3 protein. Notably, sublethal infection of naive mice with strain TC-LNS3 induced similar NS3-specific T-cell responses. These findings suggest that recombinant strains of L. monocytogenes expressing HCV antigens should prove useful for evaluating, or even inducing, protective immune responses against HCV antigens.

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Helper T cell determinant peptide contributes to induction of cellular immune responses by peptide vaccines against hepatitis C virus.

Cited by 36 publications

References 43 publications

A new era in anticancer peptide vaccines

A new era in anticancer peptide vaccines

Long Peptide Vaccination Can Lead to Lethality through CD4+ T Cell-Mediated Cytokine Storm

DNA Vaccination Protects Mice against Challenge withListeria monocytogenesExpressing the Hepatitis C Virus NS3 Protein

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