The Experts below are selected from a list of 336 Experts worldwide ranked by ideXlab platform
James Tartaglia - One of the best experts on this subject based on the ideXlab platform.
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Direct Comparison of Antigen Production and Induction of Apoptosis by Canarypox Virus- and Modified Vaccinia Virus Ankara-Human Immunodeficiency Virus Vaccine Vectors
Journal of virology, 2007Co-Authors: Xiugen Zhang, James Tartaglia, Farah Cassis-ghavami, Mike Eller, Jeffrey R. Currier, Bonnie M. Slike, Xuemin Chen, Mary Marovich, Paul SpearmanAbstract:Recombinant poxVirus vectors are undergoing intensive evaluation as vaccine candidates for a variety of infectious pathogens. AvipoxViruses, such as Canarypox Virus, are replication deficient in mammalian cells by virtue of a poorly understood species-specific restriction. Highly attenuated vaccinia Virus strains such as modified vaccinia Virus Ankara (MVA) are similarly unable to complete replication in most mammalian cells but have an abortive-late phenotype, in that the block to replication occurs post-Virus-specific DNA replication. In this study, an identical expression cassette for human immunodeficiency Virus gag, pro, and env coding sequences was placed in Canarypox Virus and MVA vector backbones in order to directly compare vector-borne expression and to analyze differences in vector-host cell interactions. Antigen production by recombinant MVA was shown to be greater than that from recombinant Canarypox Virus in the mammalian cell lines and in the primary human cells tested. This observation was primarily due to a longer duration of antigen production in recombinant MVA-infected cells. Apoptosis induction was found to be more profound with the empty Canarypox Virus vector than with MVA. Remarkably, however, the inclusion of a gag/pro/env expression cassette altered the kinetics of apoptosis induction in recombinant MVA-infected cells to levels equal to those found in Canarypox Virus-infected cells. Antigen production by MVA was noted to be greater in human dendritic cells and resulted in enhanced T-cell stimulation in an in vitro antigen presentation assay. These results reveal differences in poxVirus vector-host cell interactions that should be relevant to their use as immunization vehicles.
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Cross-Presentation by Dendritic Cells of Tumor Antigen Expressed in Apoptotic Recombinant Canarypox Virus-Infected Dendritic Cells
Journal of immunology (Baltimore Md. : 1950), 2001Co-Authors: Iris Motta, James Tartaglia, William I. Cox, Fabrice Andre, Annick Lim, Laurence Zitvogel, Eric Angevin, Philippe KourilskyAbstract:We have investigated the possible usefulness of recombinant Canarypox Virus (ALVAC) encoding the melanoma-associated Ag, Melan-A/MART-1 (MART-1), in cancer immunotherapy, using a dendritic cell (DC)-based approach. ALVAC MART-1-infected DC express, and are able to process and present, the Ag coded by the viral vector. One consistent feature of infection by ALVAC is that these Viruses induce apoptosis, and we show cross-presentation of Ag when uninfected DC are cocultured with ALVAC MART-1-infected DC. Uptake of apoptotic virally infected DC by uninfected DC and subsequent expression of tumor Ag in the latter were verified by flow cytometry analysis, image cytometry, and confocal microscopy. Functional activity was monitored in vitro by the stimulation of a MART-1-specific cytotoxic T cell clone. Heightened efficiency in Ag presentation is evidenced in the 2- to 3-fold increase in IFN-gamma production by the T cell clone, as compared with the ALVAC-infected DC alone. Cocultures of ALVAC MART-1-infected and uninfected DC are able to induce MART-1-specific T cell immune responses, as assessed by HLA class I/peptide tetramer binding, IFN-gamma ELISPOT assays, and cytotoxicity tests. Overall, our data indicate that DC infected with recombinant Canarypox Viruses may represent an efficient presentation platform for tumor Ags, which can be exploited in clinical studies.
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Canarypox Virus expressing wild type p53 for gene therapy in murine tumors mutated in p53.
Cancer gene therapy, 2001Co-Authors: Laurence Odin, James Tartaglia, Marie Favrot, Dominique Poujol, Jean-philippe Michot, Philippe Moingeon, Isabelle PuisieuxAbstract:Canarypox Virus expressing wild type p53 for gene therapy in murine tumors mutated in p53
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evaluation of gene transfer efficiency by viral vectors to murine bladder epithelium
The Journal of Urology, 2001Co-Authors: Robert D Siemens, Christopher J Austin, James Tartaglia, Timothy L. RatliffAbstract:Purpose: In pre-clinical gene therapy studies of bladder cancer there is tremendous variation in the ability of viral vectors to deliver genetic material to bladder epithelium. Possible explanations for this variability may involve the physical parameters of delivering vectors in these experimental models. We examined the effects of intravesical volume and pressure during instillation as well as chemical modification of the bladder epithelium on subsequent gene expression in the bladder in mice.Materials and Methods: Female C57B1/6 mice underwent intravesical instillation of the replication restricted Canarypox Virus (ALVAC) recombinant for the reporter genes luciferase or β-galactosidase. Similar viral titers were instilled at different volumes and a pressure transducer measured intravesical pressure when the vector was instilled. Also, various agents, including 0.6 N hydrochloric acid, 0.4% oxychlorosene, poly-L-lysine and 0.25 M. ammonium chloride, were used to modify the bladder surface before vector ...
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Induction of immune responses to HIV-1 by Canarypox Virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group.
AIDS (London England), 1998Co-Authors: Robert B Belshe, James Tartaglia, Geoffrey J Gorse, William I. Cox, Mark J. Mulligan, Thomas G. Evans, Michael C. Keefer, Jean-louis Excler, Anne-marie Duliege, James McnamaraAbstract:Objective To determine the ability of live attenuated Canarypox Virus expressing HIV antigens to induce CD8+ cytotoxic T-cell responses and to prime for neutralizing antibody responses to boosting with purified recombinant gp120 subunit vaccine. Design A prospective, double-blind, randomized, immunogenicity and safety study was conducted in healthy adults at low risk for acquiring HIV infection and who were seronegative for HIV. Methods CD8+ cytotoxic T-cells directed against Env or Gag expressing target cells were measured after live recombinant Canarypox-HIV-1 vaccine priming (vaccine given at days 0, 7, 14 and 21). Neutralizing antibodies were measured after subunit boosting (vaccine given at days 28 and 84). Results CD8+ CTL were induced in 64% of volunteers by the live recombinant Canarypox-HIV-1 vaccine. All volunteers who received two doses of subunit vaccine after live recombinant Canarypox priming developed neutralizing antibodies directed against laboratory strains of HIV-1 and seven out of eight volunteers tested developed neutralizing antibodies to the primary isolate, BZ167, but to none of eight other primary isolates. Unprimed controls had low or absent neutralizing antibodies after two doses of subunit vaccine. Conclusions The live Canarypox vector was safe, stimulated cytotoxic T-cells and primed for a vigorous neutralizing antibody response upon boosting with subunit gp120 vaccine. This vaccine combination should be evaluated further for inducing protection against HIV infection.
Enzo Paoletti - One of the best experts on this subject based on the ideXlab platform.
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Challenge of Chimpanzees Immunized with a Recombinant Canarypox-HIV-1 Virus
Virology, 1997Co-Authors: Marc Girard, James Tartaglia, Enzo Paoletti, Peter L Nara, Elna Van Der Ryst, Françoise Barré-sinoussi, Christine Blondeau, Myra Jennings, Florence Verrier, Bernard MeignierAbstract:Abstract To evaluate the potential protective efficacy of a live recombinant human immunodeficiency Virus type 1 (HIV-1) Canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant Canarypox Virus that expresses the HIV-1 IIIB(LAI) gp120/TM, gag, and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated Virus in the form of peripheral blood mononuclear cells from an HIV-1 IIIB(LAI) -infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1 IIIB(LAI) of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1 MN antigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1 DH12 , a heterologous subtype B isolate. Neither chimpanzee had neutralizing antibodies to HIV-1 DH12 , and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1 IIIB(LAI) or HIV-1 MN did not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1 DH12 .
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canine distemper Virus cdv infection of ferrets as a model for testing morbilliVirus vaccine strategies nyvac and alvac based cdv recombinants protect against symptomatic infection
Journal of Virology, 1997Co-Authors: Charles B Stephensen, James Tartaglia, Jill Taylor, Janet Welter, S R Thaker, Enzo PaolettiAbstract:Canine distemper Virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia Virus and in the ALVAC strain of Canarypox Virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-Virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies Virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-Virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other MorbilliVirus infections, including measles, this model will be useful in testing new candidate MorbilliVirus vaccines.
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Memory Cytotoxic T Lymphocyte Responses in Human Immunodeficiency Virus Type 1 (HIV-1)-Negative Volunteers Immunized with a Recombinant Canarypox Expressing gp160 of HIV-1 and Boosted with a Recombinant gp160
The Journal of infectious diseases, 1996Co-Authors: Béatrice Fleury, James Tartaglia, Enzo Paoletti, Jean-louis Excler, M P Kieny, Gilles Pialoux, Geneviève Janvier, Florence Buseyne, Michael N. Robertson, Yves RiviereAbstract:A vaccine against human immunodeficiency Virus (HIV) should induce Virus-specific cytotoxic T lymphocyte (CTL) activity. Immunization of uninfected volunteers with a Canarypox Virus express ing HIV envelope was carried out in a phase I trial. Two injections of Canarypox expressing HIV l M N gp160 (months 0 and 1) were followed by two boosts of recombinant envelope protein (months 3 and 6). HIV envelope-specific CTL were detected in peripheral blood mononuclear cells stimulated with autologous HIV-l-infected blast cells. T cell lines were obtained from 18 of 20 donors: CTL were detected at least once following immunization in 7 (39%) of these 18. This activity was mediated by major histocompatibility complex class I-restricted CD3+CD8+ T cells. For two subjects, this activity was still present 2 years after the initial immunization. The CTL responses with this prime boost regimen are the best observed with any HIV vaccine tested in humans. Vaccination against the human immunodeficiency Virus type I (HIV-I) is a key strategy for the eventual control of the AIDS pandemic. Since the discovery of the etiologic agent of AIDS, different candidate vaccines have been designed and developed, including whole killed Virus, live attenuated Virus, Virus-like particles including pseudovirions, protein subunits based on HIV structural genes, peptides based on selected im munoreactive parts of the viral proteins, live recombinant viral or bacterial vectors, and DNA-based immunogens encoding one or more HIV proteins [1-3]. Live recombinant vaccinia Viruses have been used successfully to induce protective immu nity against animal infectious diseases such as rabies [4], but because the use ofvaccinia Virus for human vaccination against smallpox has been shown to induce rare but serious complica tions [5], other recombinant poxViruses such as avian poxvi ruses have been developed [6, 7]. As was the case for most live expression vectors in AIDS vaccine studies, initial efforts have focused on products based on the HIV-I envelope protein, since several epitopes of env have been described to induce neutralizing antibodies and cell-mediated immune responses, including cytotoxic T lymphocytes (CTL). In HIV-seronegative volunteers at low risk ofHIV infection, the safety and immuno
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p53 as a target for cancer vaccines: recombinant Canarypox Virus vectors expressing p53 protect mice against lethal tumor cell challenge.
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Judith Roth, James Tartaglia, Enzo Paoletti, Dirk P. Dittmer, Delphine Rea, Arnold J. LevineAbstract:Abstract The p53 protein is an attractive target for immunotherapy, because mutations in the p53 gene are the most common genetic alterations found in human tumors. These mutations result in high levels of p53 protein in the tumor cell, whereas the expression level of wild-type p53 in nonmalignant tissue is usually much lower. Several Canarypox Virus recombinants expressing human or murine p53 in wild-type or mutant form were constructed. Immunization with these Viruses protected BALB/c mice from a challenge with an isogenic and highly tumorigenic mouse fibroblast tumor cell line expressing high levels of mutant p53. The tumor protection was equally effective regardless of whether wild-type or mutant p53 was used for the immunization, indicating that the immunologic response was not dependent on any particular p53 mutation and that immunization with this live Virus vaccine works effectively against mutant p53 protein expressed in a tumor cell. In tumors escaping immunologic rejection, the expression of the p53 protein was commonly down-regulated.
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protection of cats against feline leukemia Virus by vaccination with a Canarypox Virus recombinant alvac fl
Journal of Virology, 1993Co-Authors: J. Tartaglia, P. Desmettre, Oswald Jarrett, James C Neil, Enzo PaolettiAbstract:Two ALVAC (Canarypox Virus)-based recombinant Viruses expressing the feline leukemia Virus (FeLV) subgroup A env and gag genes were assessed for their protective efficacy in cats. Both recombinant Viruses contained the entire gag gene. ALVAC-FL also expressed the entire envelope glycoprotein, while ALVAC-FL(dl IS) expressed an env-specific gene product deleted of the putative immunosuppressive region. Although only 50% of the cats vaccinated with ALVAC-FL(dl IS) were protected against persistent viremia after oronasal exposure to a homologous FeLV isolate, all cats administered ALVAC-FL resisted the challenge exposure. Significantly, protection was afforded in the absence of detectable FeLV-neutralizing antibodies. These results represent the first effective vaccination of cats against FeLV with a poxVirus-based recombinant vector and have implications that are relevant not only to FeLV vaccine development but also to developing vaccines against other retroViruses, including human immunodeficiency Virus.
Robert Nordgren - One of the best experts on this subject based on the ideXlab platform.
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domestic goose as a model for west nile Virus vaccine efficacy
Vaccine, 2013Co-Authors: Mariana Sa E Silva, J M Minke, Robert Nordgren, Kemal Karaca, Angela E Ellis, David E SwayneAbstract:Abstract West Nile Virus (WNV) is an emergent pathogen in the Americas, first reported in New York during 1999, and has since spread across the USA, Central and South America causing neurological disease in humans, horses and some bird species, including domestic geese. No WNV vaccines are licensed in the USA for use in geese. This study reports the development of a domestic goose vaccine efficacy model, based on utilizing multiple parameters to determine protection. To test the model, 47 geese were divided in two experiments, testing five different vaccine groups and two sham groups (challenged and unchallenged). Based on the broad range of results for individual metrics between the Challenged-Sham and Unchallenged-Sham groups, the best parameters to measure protection were Clinical Pathogenicity Index (CPI), plasma Virus positive geese on days 1–4 post-inoculation and plasma Virus titers, and brain histological lesion rates and severity scores. Compared to the Challenged-Sham group, the fowlpox Virus vectored vaccine with inserts of WNV prM and E proteins (vFP2000) provided the best protection with significant differences in all five metrics, followed by the Canarypox Virus vectored vaccine with inserts of WNV prM and E proteins (vCP2018) with four metrics of protection, recombinant vCP2017 with three metrics and WNV E protein with one. These data indicate that domestic geese can be used in an efficacy model for vaccine protection studies using clinical, plasma virological and brain histopathological parameters to evaluate protection against WNV challenge.
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protective immunization of horses with a recombinant Canarypox Virus vectored vaccine co expressing genes encoding the outer capsid proteins of african horse sickness Virus
Vaccine, 2009Co-Authors: Alan John Guthrie, J M Minke, Melvyn Quan, Carina W. Lourens, Jean-christophe Audonnet, Jiansheng Yao, Robert Nordgren, Ian A. Gardner, James N MaclachlanAbstract:We describe the development and preliminary characterization of a recombinant Canarypox Virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness Virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant Canarypox Virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of Virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contrast, a horse immunized with a commercial recombinant Canarypox Virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 Viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness. AHSV was detected by Virus isolation and quantitative reverse transcriptase polymerase chain reaction in the blood of the control horse from 8 days onwards after challenge infection whereas AHSV was not detected at any time in the blood of the ALVAC-AHSV vaccinated horses. The control horse seroconverted to AHSV by 2 weeks after challenge infection as determined by both Virus neutralization and ELISA assays, whereas six of eight of the ALVAC-AHSV vaccinated horses did not seroconvert by either assay following challenge infection with virulent AHSV-4. These data confirm that the ALVAC-AHSV vaccine will be useful for the protective immunization of equids against African horse sickness, and avoids many of the problems inherent to live-attenuated AHSV vaccines.
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protective immunization of horses with a recombinant Canarypox Virus vectored vaccine co expressing genes encoding the outer capsid proteins of african horse sickness Virus
Vaccine, 2009Co-Authors: Alan John Guthrie, J M Minke, Melvyn Quan, Carina W. Lourens, Jean-christophe Audonnet, Robert Nordgren, Ian A. Gardner, Ling He, James N MaclachlanAbstract:Racing South Africa's (Pty) Ltd Equine Research Grant, the Thoroughbred Racing Trust of South Africa. Harriet E. Pfleger Foundation.
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a west nile Virus wnv recombinant Canarypox Virus vaccine elicits wnv specific neutralizing antibodies and cell mediated immune responses in the horse
Veterinary Immunology and Immunopathology, 2008Co-Authors: El H Garch, J M Minke, J C Audonnet, Robert Nordgren, Edlund C Toulemonde, J Rehder, Stephanie A Richard, S Dinic, Christine Andreoni, V JuillardAbstract:Successful vaccination against West Nile Virus (WNV) requires induction of both neutralizing antibodies and cell-mediated immune responses. In this study, we have assessed the ability of a recombinant ALVAC-WNV vaccine (RECOMBITEK WNV) to elicit neutralizing antibodies and Virus-specific cell-mediated immune responses in horses. In addition, we examined whether prior exposure to ALVAC-WNV vaccine would inhibit B and cell-mediated immune responses against the transgene product upon subsequent booster immunizations with the same vaccine. The results demonstrated that the recombinant ALVAC-WNV vaccine induced neutralizing antibodies and prM/E insert-specific IFN-gamma(+) producing cells against WNV in vaccinated horses. Prior exposure to ALVAC-WNV vaccine did not impair the ability of horses to respond to two subsequent booster injections with the same vaccine, although anti-vector-specific antibody and cell-mediated immune responses were induced in vaccinated horses. This report describes, for the first time, the induction of antigen-specific cell-mediated responses following vaccination with an ALVAC Virus recombinant vaccine encoding WNV antigens. Moreover, we showed that both WNV-specific IFN-gamma producing cells and anti-WNV neutralizing antibody responses, are not inhibited by subsequent vaccinations with the same vector vaccine.
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Recombinant Canarypox Virus vaccine co-expressing genes encoding the VP2 and VP5 outer capsid proteins of bluetongue Virus induces high level protection in sheep.
Vaccine, 2006Co-Authors: Josh D. Boone, Jean-christophe Audonnet, Jiansheng Yao, Robert Nordgren, Udeni B. R. Balasuriya, Kemal Karaca, Federica Monaco, Giovanni Savini, Ian A. GardnerAbstract:We describe the development and preliminary characterization of a recombinant Canarypox Virus vectored vaccine for protective immunization of ruminants against bluetongue Virus (BTV) infection. Sheep (n=6) immunized with recombinant Canarypox Virus vector (BTV-CP) co-expressing synthetic genes encoding the two outer capsid proteins (VP2 and VP5) of BTV serotype 17 (BTV-17) developed high titers (40-160) of Virus-specific neutralizing antibodies and were resistant to challenge with a field strain of BTV-17. In contrast, sheep (n=5) immunized with a commercial recombinant Canarypox Virus vector expressing the E and preM genes of West Nile Virus were seronegative to BTV and developed pyrexia, lymphopenia, and extended, high-titered viremias following challenge exposure to the field strain of BTV-17. These data confirm that the BTV-CP vaccine may be useful for the protective immunization of ruminants against bluetongue, and it may avoid the problems inherent to live-attenuated (LA) BTV vaccines.
J M Minke - One of the best experts on this subject based on the ideXlab platform.
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domestic goose as a model for west nile Virus vaccine efficacy
Vaccine, 2013Co-Authors: Mariana Sa E Silva, J M Minke, Robert Nordgren, Kemal Karaca, Angela E Ellis, David E SwayneAbstract:Abstract West Nile Virus (WNV) is an emergent pathogen in the Americas, first reported in New York during 1999, and has since spread across the USA, Central and South America causing neurological disease in humans, horses and some bird species, including domestic geese. No WNV vaccines are licensed in the USA for use in geese. This study reports the development of a domestic goose vaccine efficacy model, based on utilizing multiple parameters to determine protection. To test the model, 47 geese were divided in two experiments, testing five different vaccine groups and two sham groups (challenged and unchallenged). Based on the broad range of results for individual metrics between the Challenged-Sham and Unchallenged-Sham groups, the best parameters to measure protection were Clinical Pathogenicity Index (CPI), plasma Virus positive geese on days 1–4 post-inoculation and plasma Virus titers, and brain histological lesion rates and severity scores. Compared to the Challenged-Sham group, the fowlpox Virus vectored vaccine with inserts of WNV prM and E proteins (vFP2000) provided the best protection with significant differences in all five metrics, followed by the Canarypox Virus vectored vaccine with inserts of WNV prM and E proteins (vCP2018) with four metrics of protection, recombinant vCP2017 with three metrics and WNV E protein with one. These data indicate that domestic geese can be used in an efficacy model for vaccine protection studies using clinical, plasma virological and brain histopathological parameters to evaluate protection against WNV challenge.
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an african horse sickness Virus serotype 4 recombinant Canarypox Virus vaccine elicits specific cell mediated immune responses in horses
Veterinary Immunology and Immunopathology, 2012Co-Authors: El H Garch, Alan John Guthrie, V. Cozette, L Lemaitre, Jan Ernst Crafford, P. Amouyal, P.y. Durand, Edlund C Toulemonde, J M MinkeAbstract:A recombinant Canarypox Virus vectored vaccine co-expressing synthetic genes encoding outer capsid proteins, VP2 and VP5, of African horse sickness Virus (AHSV) serotype 4 (ALVAC®–AHSV4) has been demonstrated to fully protect horses against homologous challenge with virulent field Virus. Guthrie et al. (2009) detected weak and variable titres of neutralizing antibody (ranging from <10 to 40) 8 weeks after vaccination leading us to hypothesize that there could be a participation of cell mediated immunity (CMI) in protection against AHSV4. The present study aimed at characterizing the CMI induced by the experimental ALVAC®–AHSV4 vaccine. Six horses received two vaccinations twenty-eight days apart and three horses remained unvaccinated. The detection of VP2/VP5 specific IFN-γ responses was assessed by enzyme linked immune spot (ELISpot) assay and clearly demonstrated that all ALVAC®–AHSV4 vaccinated horses developed significant IFN-γ production compared to unvaccinated horses. More detailed immune responses obtained by flow cytometry demonstrated that ALVAC®–AHSV4 vaccinations induced immune cells, mainly CD8+ T cells, able to recognize multiple T-epitopes through all VP2 and only the N-terminus sequence of VP5. Neither VP2 nor VP5 specific IFN-γ responses were detected in unvaccinated horses. Overall, our data demonstrated that an experimental recombinant Canarypox based vaccine induced significant CMI specific for both VP2 and VP5 proteins of AHSV4.
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protective immunization of horses with a recombinant Canarypox Virus vectored vaccine co expressing genes encoding the outer capsid proteins of african horse sickness Virus
Vaccine, 2009Co-Authors: Alan John Guthrie, J M Minke, Melvyn Quan, Carina W. Lourens, Jean-christophe Audonnet, Jiansheng Yao, Robert Nordgren, Ian A. Gardner, James N MaclachlanAbstract:We describe the development and preliminary characterization of a recombinant Canarypox Virus vectored (ALVAC) vaccine for protective immunization of equids against African horse sickness Virus (AHSV) infection. Horses (n=8) immunized with either of two concentrations of recombinant Canarypox Virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of Virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contrast, a horse immunized with a commercial recombinant Canarypox Virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 Viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness. AHSV was detected by Virus isolation and quantitative reverse transcriptase polymerase chain reaction in the blood of the control horse from 8 days onwards after challenge infection whereas AHSV was not detected at any time in the blood of the ALVAC-AHSV vaccinated horses. The control horse seroconverted to AHSV by 2 weeks after challenge infection as determined by both Virus neutralization and ELISA assays, whereas six of eight of the ALVAC-AHSV vaccinated horses did not seroconvert by either assay following challenge infection with virulent AHSV-4. These data confirm that the ALVAC-AHSV vaccine will be useful for the protective immunization of equids against African horse sickness, and avoids many of the problems inherent to live-attenuated AHSV vaccines.
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protective immunization of horses with a recombinant Canarypox Virus vectored vaccine co expressing genes encoding the outer capsid proteins of african horse sickness Virus
Vaccine, 2009Co-Authors: Alan John Guthrie, J M Minke, Melvyn Quan, Carina W. Lourens, Jean-christophe Audonnet, Robert Nordgren, Ian A. Gardner, Ling He, James N MaclachlanAbstract:Racing South Africa's (Pty) Ltd Equine Research Grant, the Thoroughbred Racing Trust of South Africa. Harriet E. Pfleger Foundation.
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a west nile Virus wnv recombinant Canarypox Virus vaccine elicits wnv specific neutralizing antibodies and cell mediated immune responses in the horse
Veterinary Immunology and Immunopathology, 2008Co-Authors: El H Garch, J M Minke, J C Audonnet, Robert Nordgren, Edlund C Toulemonde, J Rehder, Stephanie A Richard, S Dinic, Christine Andreoni, V JuillardAbstract:Successful vaccination against West Nile Virus (WNV) requires induction of both neutralizing antibodies and cell-mediated immune responses. In this study, we have assessed the ability of a recombinant ALVAC-WNV vaccine (RECOMBITEK WNV) to elicit neutralizing antibodies and Virus-specific cell-mediated immune responses in horses. In addition, we examined whether prior exposure to ALVAC-WNV vaccine would inhibit B and cell-mediated immune responses against the transgene product upon subsequent booster immunizations with the same vaccine. The results demonstrated that the recombinant ALVAC-WNV vaccine induced neutralizing antibodies and prM/E insert-specific IFN-gamma(+) producing cells against WNV in vaccinated horses. Prior exposure to ALVAC-WNV vaccine did not impair the ability of horses to respond to two subsequent booster injections with the same vaccine, although anti-vector-specific antibody and cell-mediated immune responses were induced in vaccinated horses. This report describes, for the first time, the induction of antigen-specific cell-mediated responses following vaccination with an ALVAC Virus recombinant vaccine encoding WNV antigens. Moreover, we showed that both WNV-specific IFN-gamma producing cells and anti-WNV neutralizing antibody responses, are not inhibited by subsequent vaccinations with the same vector vaccine.
Philippe Moingeon - One of the best experts on this subject based on the ideXlab platform.
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Safety of intravenous administration of a Canarypox Virus encoding the human wild-type p53 gene in colorectal cancer patients
Cancer Gene Therapy, 2003Co-Authors: Anand G Menon, Marieclaude Bonnet, Peter J K Kuppen, Sjoerd H Van Der Burg, Rienk Offringa, Bert I J Harinck, Rob A E M Tollenaar, Anke Redeker, Hein Putter, Philippe MoingeonAbstract:Overexpression of p53 occurs in more than 50% of colorectal cancers. Therefore, p53 represents an attractive target antigen for immunotherapy. We assessed the safety of a Canarypox Virus encoding the human wild-type p53 gene given intravenously to end-stage colorectal cancer patients in a three-step dose escalation study aimed at inducing p53 immune responses. Patients with metastatic disease of p53-overexpressing colorectal cancers were vaccinated three times at 3-week intervals, each time with 10^6.5 CCID_50 (CCID_50=cell culture infectious dose 50%; group 1, n =5), 10^7.0 CCID_50 (group 2, n =5) or 10^7.5 CCID_50 (group 3, n =6). Vital signs and the occurrence of adverse events were monitored and blood was analyzed for biochemical and hematological parameters as well as signs of auto-immune safety. In all, 16 patients were enrolled and 15 patients completed three vaccinations. No anaphylactic reaction or unwanted auto-immune reactions were observed. A total of 16 serious adverse events (SAEs) occurred: 10 in group 1, three in group 2 and three in group 3. All SAEs were tumor-related complications. There was no difference in the frequency of adverse events between the three groups, except for fever. Fever was the only vaccination-related adverse event consistently observed and was most frequent and outspoken in the group 3 patients. The majority was a grade 1 or 2 fever (93%) and grade 3 fever (7%) was observed in three patients of group 3. Some patients showed humoral and cellular responses against p53, following vaccinations. After having completed his initial treatment cycle, one patient (group 2) received a second treatment cycle of three doses of 10^7.5 CCID_50 and subsequently showed stable disease. All other patients showed progressive disease. We conclude that ALVAC-p53 can be administered intravenously to colorectal cancer patients without serious toxicity or pathological autoimmunity and can induce immune responses against p53.
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immunization of colorectal carcinoma patients with a recombinant Canarypox Virus expressing the tumor antigen ep cam ksa alvac ksa and granulocyte macrophage colony stimulating factor induced a tumor specific cellular immune response
Clinical Cancer Research, 2003Co-Authors: Gustav J Ullenhag, Marieclaude Bonnet, Philippe Moingeon, Janerik Frodin, Szilvia Mosolits, Shahryar Kiaii, Moustapha Hassan, Hakan Mellstedt, Hodjattallah RabbaniAbstract:PURPOSE: Colorectal carcinoma cells express the tumor-associated antigen epithelial cellular adhesion molecule (Ep-CAM)/KSA. Passive immunotherapy with monoclonal antibodies using this antigen has ...
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Canarypox Virus expressing wild type p53 for gene therapy in murine tumors mutated in p53.
Cancer gene therapy, 2001Co-Authors: Laurence Odin, James Tartaglia, Marie Favrot, Dominique Poujol, Jean-philippe Michot, Philippe Moingeon, Isabelle PuisieuxAbstract:Canarypox Virus expressing wild type p53 for gene therapy in murine tumors mutated in p53
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Canarypox Virus-mediated interleukin 12 gene transfer into murine mammary adenocarcinoma induces tumor suppression and long-term antitumoral immunity.
Human gene therapy, 1998Co-Authors: Isabelle Puisieux, James Tartaglia, William I. Cox, Laurence Odin, Dominique Poujol, Philippe Moingeon, Marie FavrotAbstract:ABSTRACT The antitumoral activity of recombinant Canarypox Virus vectors (ALVAC) expressing murine interleukin 12 (IL-12) was evaluated in the syngeneic, nonimmunogenic murine mammary adenocarcinom...