Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin

ABSTRACT In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an immunogenic simian immunodeficiency virus gag DNA vaccine elicited high-frequency CTL responses specific for all of the epitopes included in the vaccine. Both multiepitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant modified vaccinia virus Ankara vaccines expressing complete viral proteins. The natural hierarchy of immunodominance for these epitopes was clearly evident in the boosted monkeys. These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance.

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Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses

Journal of Virology ◽

10.1128/jvi.75.21.10139-10148.2001 ◽

2001 ◽

Vol 75 (21) ◽

pp. 10139-10148 ◽

Cited By ~ 45

Author(s):

Wei Shi ◽

Jianzhong Liu ◽

Yujun Huang ◽

Liang Qiao

Keyword(s):

Dna Vaccine ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Oral Immunization ◽

Lymphocytic Choriomeningitis ◽

Lymphoid Tissues ◽

Adjuvant Effect ◽

Ctl Response ◽

Lymphocyte Responses ◽

Ctl Responses

ABSTRACT Intestinal mucosa is a portal for many infectious pathogens. Systemic immunization, in general, does not induce a cytotoxic T-lymphocyte (CTL) response at the mucosal surface. Because papillomavirus (PV) naturally infects mucosa and skin, we determined whether PV pseudovirus, i.e., PV-like particles in which unrelated DNA plasmids are packaged, could generate specific mucosal immunity. We found that the pseudovirus that encoded the lymphocytic choriomeningitis virus gp33 epitope induced a stronger CTL response than a DNA vaccine (plasmid) encoding the same epitope given systemically. The virus-like particles that were used to make the pseudoviruses provided an adjuvant effect for induction of CTLs by the DNA vaccine. The PV pseudovirus pseudoinfected mucosal and systemic lymphoid tissues when administered orally. Oral immunization with the pseudovirus encoding human PV type 16 mutant E7 induced mucosal and systemic CTL responses. In comparison, a DNA vaccine encoding E7, when given orally, did not induce a CTL response in intestinal mucosal lymphoid tissue. Further, oral immunization with the human PV pseudovirus encoding E7 protected mice against mucosal challenge with an E7-expressing bovine PV pseudovirus. Thus, PV pseudovirus can be used as a novel vaccine to induce mucosal and systemic CTL responses.

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Codon Modified Human Papillomavirus Type 16 E7 DNA Vaccine Enhances Cytotoxic T-Lymphocyte Induction and Anti-tumour Activity

Virology ◽

10.1006/viro.2002.1584 ◽

2002 ◽

Vol 301 (1) ◽

pp. 43-52 ◽

Cited By ~ 57

Author(s):

Wen Jun Liu ◽

Fengguang Gao ◽

Kong Nan Zhao ◽

Weiming Zhao ◽

Germain J.G. Fernando ◽

...

Keyword(s):

Human Papillomavirus ◽

Dna Vaccine ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Human Papillomavirus Type 16 ◽

Anti Tumour Activity ◽

Tumour Activity

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Suppression of antitumour protective cytotoxic T lymphocyte responses to a human papillomavirus 16 E7 DNA vaccine by coinjection of interleukin-12 complementary DNA: involvement of nitric oxide in immune suppression

Immunology ◽

10.1111/j.1365-2567.2009.03068.x ◽

2009 ◽

Vol 128 (1pt2) ◽

pp. e707-e717 ◽

Cited By ~ 10

Author(s):

Jeong-Im Sin

Keyword(s):

Nitric Oxide ◽

Human Papillomavirus ◽

Dna Vaccine ◽

T Lymphocyte ◽

Immune Suppression ◽

Cytotoxic T Lymphocyte ◽

Interleukin 12 ◽

Complementary Dna ◽

Human Papillomavirus 16 ◽

Lymphocyte Responses

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Characterization of cytotoxic T-lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD-integrin-binding motif

Journal of Medical Virology ◽

10.1002/jmv.21571 ◽

2009 ◽

Vol 81 (7) ◽

pp. 1131-1139 ◽

Cited By ~ 6

Author(s):

W.P. Poh ◽

T. Narasaraju ◽

N.A. Pereira ◽

F. Zhong ◽

M.C. Phoon ◽

...

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Binding Motif ◽

Sars Coronavirus

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Enhanced in vivo gene expression mediated by listeriolysin O incorporated anionic LPDII: Its utility in cytotoxic T lymphocyte-inducing DNA vaccine

Journal of Controlled Release ◽

10.1016/j.jconrel.2010.06.017 ◽

2010 ◽

Vol 148 (2) ◽

pp. 219-225 ◽

Cited By ~ 10

Author(s):

Xun Sun ◽

Chester Provoda ◽

Kyung-Dall Lee

Keyword(s):

Gene Expression ◽

Dna Vaccine ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Listeriolysin O

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Induction of Immune Tolerance in Asthmatic Mice by Vaccination with DNA Encoding an Allergen–Cytotoxic T Lymphocyte-Associated Antigen 4 Combination

Clinical and Vaccine Immunology ◽

10.1128/cvi.00434-10 ◽

2011 ◽

Vol 18 (5) ◽

pp. 807-814 ◽

Cited By ~ 7

Author(s):

Fang Zhang ◽

Gang Huang ◽

Bo Hu ◽

Yong Song ◽

Yi Shi

Keyword(s):

Airway Inflammation ◽

Dna Vaccine ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Treg Cells ◽

Airway Hyperreactivity ◽

Interleukin 4 ◽

High Dose ◽

Dna Encoding ◽

Allergen Specific Immunotherapy

ABSTRACTAllergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen–cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA3.1) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed and transfected into COS-7 cells to obtain the fusion protein OVA-CTLA-4, which was able to bind the B7 ligand on dendritic cells (DCs), and induced CD25+Foxp3+regulatory T (Treg) cells by the coculture of naive CD4+T cells with DCsin vitro. In an animal study, BALB/c mice were sensitized and challenged with OVA to establish the asthmatic model. Vaccination with a high dose of OVA-CTLA-4-pcDNA3.1significantly decreased interleukin-4 (IL-4) and IL-5 levels and eosinophil counts and prevented OVA-induced reduction of the gamma interferon level in the bronchoalveolar lavage fluid. In addition, these mice suffered less severe airway inflammation and had lower levels of OVA-specific IgE and IgG1 titers in serum. Also, high-dose OVA-CTLA-4-pcDNA3.1vaccination inhibited the development of airway hyperreactivity and prevented OVA-induced reduction of the percentages of Foxp3+Treg cells in the spleen. Our results indicate that a high dose of allergen-CTLA-4-encoding DNA vaccine was more effective in preventing an allergen-induced Th2-skewed immune response through the induction of Treg cells and may be a new alternative therapy for asthma.

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A DNA Vaccine Coding for the Brucella Outer Membrane Protein 31 Confers Protection against B. melitensis and B. ovis Infection by Eliciting a Specific Cytotoxic Response

Infection and Immunity ◽

10.1128/iai.73.10.6537-6546.2005 ◽

2005 ◽

Vol 73 (10) ◽

pp. 6537-6546 ◽

Cited By ~ 65

Author(s):

Juliana Cassataro ◽

Carlos A. Velikovsky ◽

Silvia de la Barrera ◽

Silvia M. Estein ◽

Laura Bruno ◽

...

Keyword(s):

T Cells ◽

Outer Membrane ◽

Dna Vaccine ◽

Cytotoxic T Lymphocyte ◽

Protective Efficacy ◽

Outer Membrane Proteins ◽

Humoral Response ◽

T Cell Subsets

ABSTRACT The development of an effective subunit vaccine against brucellosis is a research area of intense interest. The outer membrane proteins (Omps) of Brucella spp. have been extensively characterized as potential immunogenic and protective antigens. This study was conducted to evaluate the immunogenicity and protective efficacy of the B. melitensis Omp31 gene cloned in the pCI plasmid (pCIOmp31). Immunization of BALB/c mice with pCIOmp31 conferred protection against B. ovis and B. melitensis infection. Mice vaccinated with pCIOmp31 developed a very weak humoral response, and in vitro stimulation of their splenocytes with recombinant Omp31 did not induced the secretion of gamma interferon. Splenocytes from Omp31-vaccinated animals induced a specific cytotoxic-T-lymphocyte activity, which leads to the in vitro lysis of Brucella-infected macrophages. pCIOmp31 immunization elicited mainly CD8+ T cells, which mediate cytotoxicity via perforins, but also CD4+ T cells, which mediate lysis via the Fas-FasL pathway. In vivo depletion of T-cell subsets showed that the pCIOmp31-induced protection against Brucella infection is mediated predominantly by CD8+ T cells, although CD4+T cells also contribute. Our results demonstrate that the Omp31 DNA vaccine induces cytotoxic responses that have the potential to contribute to protection against Brucella infection. The protective response could be related to the induction of CD8+ T cells that eliminate Brucella-infected cells via the perforin pathway.

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