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Enzo Paoletti - One of the best experts on this subject based on the ideXlab platform.

  • Challenge of Chimpanzees Immunized with a Recombinant Canarypox-HIV-1 Virus
    Virology, 1997
    Co-Authors: Marc Girard, James Tartaglia, Enzo Paoletti, Peter L Nara, Elna Van Der Ryst, Françoise Barré-sinoussi, Christine Blondeau, Myra Jennings, Florence Verrier, Bernard Meignier
    Abstract:

    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 .

  • The safety and use of Canarypox vectored vaccines
    Developments in biological standardization, 1995
    Co-Authors: Stanley A. Plotkin, James Tartaglia, Michel Cadoz, Bernard Meignier, Claude Meric, O Leroy, J L Excler, Enzo Paoletti, Eva Gonczol, G. Chappuis
    Abstract:

    ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for Canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of Canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds.

  • Biological and immunogenic properties of a Canarypox-rabies recombinant, ALVAC-RG (vCP65) in non-avian species.
    Vaccine, 1995
    Co-Authors: Jill Taylor, James Tartaglia, Bernard Meignier, Bernard Languet, J. Vanderhoeven, Genoveffa Franchini, Charles V. Trimarchi, Enzo Paoletti
    Abstract:

    A Canarypox-based (ALVAC) recombinant expressing the rabies G glycoprotein has been utilized to assess in vitro and in vivo biological properties of the Canarypox virus vector system. In vitro studies have shown that no replication of the virus can be detected on six human-derived cell lines, nor can the virus be readily adapted to replicate on non-avian cells. Expression of the rabies G can be detected on all cell lines analyzed in the absence of productive viral replication. Analysis of viral-specific DNA accumulation indicated that the block in the replication cycle in the human cell lines analyzed occurred prior to DNA replication. The exact nature of the block, however, remains unknown. The concept of using a non-replicating immunization vehicle has been demonstrated through extensive in vivo studies in a range of species including non-human primates and humans. The results of such in vivo studies have exemplified the safety and immunogenicity of the ALVAC vaccine vector.

  • Preclinical evaluation of an ALVAC (Canarypox)--human cytomegalovirus glycoprotein B vaccine candidate.
    Vaccine, 1995
    Co-Authors: Eva Gonczol, Claude Meric, Enzo Paoletti, Klara Berencsi, Steve Pincus, Valéria Endrész, Stanley A. Plotkin
    Abstract:

    Successful vaccination against the human cytomegalovirus (HCMV) requires induction of both neutralizing antibody and cytotoxic T lymphocyte (CTL) responses. The HCMV glycoprotein B (gB, UL55) would be one of the most important immunogens to induce neutralizing antibodies. We tested the immunogenicity of an ALVAC (Canarypox)-HCMV-gB (ALVAC-gB) recombinant in mice and guinea pigs in order to provide preclinical data for a phase I clinical trial of a HCMV vaccine candidate. ALVAC is an attenuated vaccine strain of Canarypox virus which replicates productively in avian species but abortively in mammalian cells. The ALVAC-gB recombinant inoculated subcutaneously in mice and intramuscularly in guinea pigs induced HCMV-specific neutralizing antibodies and gB-specific CTL responses. Ultraviolet irradiation of the ALVAC-gB recombinant before immunization diminished CTL responses, indicating that intracellular expression and processing of gB-protein were necessary for CTL induction. Prior immunity to vaccinia virus did not decrease immunogenicity of the ALVAC-gB recombinant in mice. Thus, despite its host range restriction, ALVAC-gB is potentially capable of inducing both humoral and cell-mediated immune responses to HCMV in both vaccinia-immune and non-immune individuals.

  • applications of Canarypox alvac vectors in human and veterinary vaccination
    Developments in biological standardization, 1994
    Co-Authors: J. Taylor, James Tartaglia, G. Chappuis, M Riviere, C Duret, B Languet, Enzo Paoletti
    Abstract:

    This paper presents data derived from safety and efficacy studies of ALVAC-based rabies and feline leukemia virus (FeLV) vaccine candidates in target species. Inoculation of the ALVAC-RG recombinant was well tolerated in all species including humans and very young dogs. Protection induced in dogs against rabies challenge was long-lasting and could be elicited in the face of high levels of maternally-derived neutralizing antibody. Parenteral inoculation of cats with an ALVAC-FeLV recombinant was safe and induced protection against persistent infection following oro-nasal FeLV challenge.

Jules Maarten Minke - One of the best experts on this subject based on the ideXlab platform.

  • Development and Efficacy of the Recombinant Canarypox‐Based Equine Influenza (EI) Vaccine Updated According to the Last OIE Expert Surveillance Panel Recommendations
    Equine Veterinary Journal, 2014
    Co-Authors: Romain Paillot, Laurent Lemaitre, Agnes Dancer, J‐c. Thibault, Jules Maarten Minke
    Abstract:

    Reasons for performing study Since 2010, the OIE expert surveillance panel (ESP) recommends that EI vaccines contain representative equine influenza virus (EIV) strains from the Florida clade 1 and 2 sub-lineages for optimal protection against EIV currently circulating worldwide. To date, no EI vaccine commercially available in the EU meets this recommendation. Objectives This report summarises the development process of a fully updated recombinant Canarypox-based EI vaccine, including clinical efficacy results against EIV strain A/eq/Richmond/1/07. Study design The EI vaccine ProteqFlu containing 2 recombinant Canarypox viruses expressing the haemagglutinin of EIV strains was updated by replacing the A/eq/Newmarket/2/93 strain with the A/eq/Richmond/1/07 isolate (Florida clade 2 sub-lineage) and keeping A/eq/Ohio/03 (Florida clade 1 sub-lineage), to meet the last OIE recommendations. The updated EI vaccine was tested for efficacy in the Welsh mountain pony model. Methods The mode of action, production steps and efficacy of the updated EI vaccine will be presented. Efficacy was tested in a group of 7 ponies vaccinated twice, 5 weeks apart. Protective antibody response were measured and challenged by experimental infection with the A/eq/Richmond/1/07 EIV strain. Clinical signs of disease and virus shedding were compared with control unvaccinated ponies (n = 7). Results Significant protection was measured in vaccinated ponies, which supports the vaccine registration. Conclusions The recombinant Canarypox-based EI vaccine was already the first EI vaccine to meet the 2004 OIE ESP recommendations and was successfully used in Australia during the 2007 EI outbreak. This new version will be the first fully updated EI vaccine available in the EU, which will help to minimise the increasing risk of vaccine breakdown due to constant EIV evolution through antigenic drift. EI vaccination remains one of the most effective tools to prevent or limit the impact of EI, as clearly illustrated by the limited frequency and scale of EI outbreaks. Ethical animal research: All animal work received ethical approval. Sources of funding: The study was funded by Merial SAS. Competing interests: R.P. reports no conflict of interest. L.L., A.D., J-L.T. and J.M. are employed by the study sponsor.

  • development and efficacy of the recombinant Canarypox based equine influenza ei vaccine updated according to the last oie expert surveillance panel recommendations
    Equine Veterinary Journal, 2014
    Co-Authors: Romain Paillot, Laurent Lemaitre, Agnes Dancer, Jc Thibault, Jules Maarten Minke
    Abstract:

    Reasons for performing study Since 2010, the OIE expert surveillance panel (ESP) recommends that EI vaccines contain representative equine influenza virus (EIV) strains from the Florida clade 1 and 2 sub-lineages for optimal protection against EIV currently circulating worldwide. To date, no EI vaccine commercially available in the EU meets this recommendation. Objectives This report summarises the development process of a fully updated recombinant Canarypox-based EI vaccine, including clinical efficacy results against EIV strain A/eq/Richmond/1/07. Study design The EI vaccine ProteqFlu containing 2 recombinant Canarypox viruses expressing the haemagglutinin of EIV strains was updated by replacing the A/eq/Newmarket/2/93 strain with the A/eq/Richmond/1/07 isolate (Florida clade 2 sub-lineage) and keeping A/eq/Ohio/03 (Florida clade 1 sub-lineage), to meet the last OIE recommendations. The updated EI vaccine was tested for efficacy in the Welsh mountain pony model. Methods The mode of action, production steps and efficacy of the updated EI vaccine will be presented. Efficacy was tested in a group of 7 ponies vaccinated twice, 5 weeks apart. Protective antibody response were measured and challenged by experimental infection with the A/eq/Richmond/1/07 EIV strain. Clinical signs of disease and virus shedding were compared with control unvaccinated ponies (n = 7). Results Significant protection was measured in vaccinated ponies, which supports the vaccine registration. Conclusions The recombinant Canarypox-based EI vaccine was already the first EI vaccine to meet the 2004 OIE ESP recommendations and was successfully used in Australia during the 2007 EI outbreak. This new version will be the first fully updated EI vaccine available in the EU, which will help to minimise the increasing risk of vaccine breakdown due to constant EIV evolution through antigenic drift. EI vaccination remains one of the most effective tools to prevent or limit the impact of EI, as clearly illustrated by the limited frequency and scale of EI outbreaks. Ethical animal research: All animal work received ethical approval. Sources of funding: The study was funded by Merial SAS. Competing interests: R.P. reports no conflict of interest. L.L., A.D., J-L.T. and J.M. are employed by the study sponsor.

  • an african horse sickness virus serotype 4 recombinant Canarypox virus vaccine elicits specific cell mediated immune responses in horses
    Veterinary Immunology and Immunopathology, 2012
    Co-Authors: El H Garch, Alan John Guthrie, V. Cozette, L Lemaitre, Jan Ernst Crafford, P. Amouyal, P.y. Durand, Edlund C Toulemonde, Jules Maarten Minke
    Abstract:

    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.

  • An African horse sickness virus serotype 4 recombinant Canarypox virus vaccine elicits specific cell-mediated immune responses in horses.
    Veterinary Immunology and Immunopathology, 2012
    Co-Authors: H. El Garch, Alan John Guthrie, C. Edlund Toulemonde, V. Cozette, L Lemaitre, Jan Ernst Crafford, P. Amouyal, P.y. Durand, Jules Maarten Minke
    Abstract:

    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

  • evaluation of the response to an accelerated immunisation schedule using a Canarypox vectored equine influenza vaccine shortened interdose intervals and vaccination of young foals
    Australian Veterinary Journal, 2011
    Co-Authors: Jules Maarten Minke, V. Cozette, C M Elhage, P Tazawa, David Homer, L Lemaitre, J R Gilkerson, P D Kirkland
    Abstract:

    The results of an accelerated immunisation schedule for horses used as part of the emergency response plan to contain and eradicate equine influenza in Australia in 2007 is described. The horses studied were vaccinated with a recombinant Canarypox-vectored vaccine (ProteqFlu®, Merial) with a shorter interdose interval. Vaccinated horses included foals aged less than 4 months.

James Tartaglia - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of Murine Prostate Tumor Growth and Activation of Immunoregulatory Cells With Recombinant Canarypox Viruses
    2015
    Co-Authors: Thomas S. Griffith, James Tartaglia, Mutsushi Kawakita, Jun Tian, Julie Ritchey, Inder Sehgal, Timothy C. Thompson, Weicheng Zhao, Timothy L. Ratliff
    Abstract:

    Background: Immunization with modified tumor cells car-rying recombinant immunomodulatory genes is being ex-plored as cancer immunotherapy. In this study, we examine whether Canarypox ALVAC viruses carrying immunostim-ulatory cytokine genes (granulocyte–macrophage colony-stimulating factor, interleukin 2, interleukin 12, and tumor necrosis factor-) can induce antitumor immunity (to re-challenge) in the RM-1 model of a highly aggressive, weakly immunogenic murine prostate cancer. Methods: For antitu-mor activity studies, RM-1 murine prostate cancer cells were infected with the parental ALVAC virus or one or two re-combinant ALVAC–cytokine viruses and then injected into male C57BL/6 mice. For rechallenge studies, other mice were first given an injection subcutaneously with irradiated (nonproliferating) recombinant ALVAC-infected RM-1 cell

  • 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, 2007
    Co-Authors: Xiugen Zhang, James Tartaglia, Farah Cassis-ghavami, Mike Eller, Jeffrey R. Currier, Bonnie M. Slike, Xuemin Chen, Mary Marovich, Paul Spearman
    Abstract:

    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.

  • Cross-Presentation by Dendritic Cells of Tumor Antigen Expressed in Apoptotic Recombinant Canarypox Virus-Infected Dendritic Cells
    Journal of immunology (Baltimore Md. : 1950), 2001
    Co-Authors: Iris Motta, James Tartaglia, William I. Cox, Fabrice Andre, Annick Lim, Laurence Zitvogel, Eric Angevin, Philippe Kourilsky
    Abstract:

    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.

  • Canarypox virus expressing wild type p53 for gene therapy in murine tumors mutated in p53.
    Cancer gene therapy, 2001
    Co-Authors: Laurence Odin, James Tartaglia, Marie Favrot, Dominique Poujol, Jean-philippe Michot, Philippe Moingeon, Isabelle Puisieux
    Abstract:

    Canarypox virus expressing wild type p53 for gene therapy in murine tumors mutated in p53

  • 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), 1998
    Co-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 Mcnamara
    Abstract:

    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.

Jean-christophe Audonnet - One of the best experts on this subject based on the ideXlab platform.

  • 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, 2009
    Co-Authors: Alan John Guthrie, Jules Maarten Minke, Melvyn Quan, Carina W. Lourens, Jean-christophe Audonnet, Jiansheng Yao, Robert Nordgren, Ian A. Gardner, James N Maclachlan
    Abstract:

    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.

  • 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, 2009
    Co-Authors: Alan John Guthrie, Jules Maarten Minke, Melvyn Quan, Carina W. Lourens, Jean-christophe Audonnet, Jiansheng Yao, Robert Nordgren, Ian A. Gardner, N. James Maclachlan
    Abstract:

    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 (

  • Development and registration of recombinant veterinary vaccines. The example of the Canarypox vector platform
    Vaccine, 2006
    Co-Authors: Hervé Poulet, Jules Maarten Minke, Maria Camila Pardo, V. Juillard, Bob Nordgren, Jean-christophe Audonnet
    Abstract:

    The Canarypox vaccine vector (ALVAC) technology has been used to develop and license several vaccines for companion animals and horses in the European Union and USA. ALVAC is a ubiquitous vector with high biosafety since it is non-replicative in mammalians, is genetically and physically stable, and able to induce both humoral and cell-mediated immune responses against the expressed transgene product. Specific rules apply for the development and registration of recombinant vector vaccines. The biology of the vector as well as the recombinant virus must be thoroughly documented to allow the risk assessment of its use in the target species. In particular, its safety for the host and the environment must be extensively demonstrated before field trials can be authorized.

  • 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, 2006
    Co-Authors: Josh D. Boone, Jean-christophe Audonnet, Jiansheng Yao, Robert Nordgren, Udeni B. R. Balasuriya, Kemal Karaca, Federica Monaco, Giovanni Savini, Ian A. Gardner
    Abstract:

    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.

  • assessment of the efficacy of a single dose of a recombinant vaccine against west nile virus in response to natural challenge with west nile virus infected mosquitoes in horses
    American Journal of Veterinary Research, 2004
    Co-Authors: Leonardo Siger, Jean-christophe Audonnet, Robert Nordgren, Kemal Karaca, Richard A Bowen, Michael J Murray, Paul Gordy, Sheena M Loosmore, Jules Maarten Minke
    Abstract:

    Objective—To determine the onset of immunity after IM administration of a single dose of a recombinant Canarypox virus vaccine against West Nile virus (WNV) in horses in a blind challenge trial. Animals—20 mixed-breed horses. Procedure—Horses with no prior exposure to WNV were randomly assigned to 1 of 2 groups (10 horses/group). In 1 group, a recombinant Canarypox virus vaccine against WNV was administered to each horse once (day 0). The other 10 control horses were untreated. On day 26, 9 treated and 10 control horses were challenged via the bites of mosquitoes (Aedes albopictus) infected with WNV. Clinical responses and WNV isolation were monitored for 14 days after challenge exposure; antibody responses against WNV after administration of the vaccine and challenge were also assessed in both groups. Results—Following challenge via WNV-infected mosquitoes, 1 of 9 treated horses developed viremia. In contrast, 8 of 10 control horses developed viremia after challenge exposure to WNV-infected mosquitoes. A...

Michael C. Keefer - One of the best experts on this subject based on the ideXlab platform.

  • Phase 2 Study of an HIV-1 Canarypox Vaccine (vCP1452) Alone and in Combination With rgp120: Negative Results Fail to Trigger a Phase 3 Correlates Trial
    Journal of acquired immune deficiency syndromes (1999), 2007
    Co-Authors: Nina D. Russell, Michael C. Keefer, M. Juliana Mcelrath, Kent J. Weinhold, David C. Montefiori, Barney S. Graham, Steve Self, Guido Ferrari, Helen Horton, Georgia D. Tomaras
    Abstract:

    The development of a preventive HIV vaccine is the best long-term solution to controlling HIV and AIDS. Multiple approaches to vaccine development are being pursued and include DNA, viral vector, protein, or peptide-based vaccines, alone or in combination. The attenuated poxvirus vectors, particularly the Canarypox (ALVAC) vectors, have been some of the most extensively studied. An ALVAC gp160 product was the first replication-incompetent HIV vaccine to demonstrate consistent CD8+ cytotoxic T lymphocyte (CTL) responses after vaccination of seronegative persons.1 Subsequent Canarypox vaccine candidates were developed to increase expression of more complex HIV-1 gene inserts, and these have undergone extensive evaluation.2–7 The most recent generation of Canarypox HIV vaccines, the ALVAC-HIV vCP1452, encodes HIV-1 gp120, the entire Gag protein, a portion of pol, and several human CTL epitopes from nef and pol. It also contains sequences encoding the E3L and K3L vaccinia proteins,8 which are known to inhibit apoptosis and prolong protein expression in human cells.9 In cell culture, vCP1452 demonstrates efficient protein expression, which is enhanced significantly over the earlier generation Canarypox vector, vCP205.9 Five Canarypox vaccines were previously evaluated in 9 different AIDS Vaccine Evaluation Group (AVEG) trials with or without rgp120 or rgp160 in high- and low-risk volunteers and demonstrated a favorable safety profile.1–5,7 The 4 to 6 immunizations administered in these studies elicited neutralizing antibodies to homologous HIV-1 strains in 88% of participants and CD8+ CTLs to Env and/or Gag epitopes in up to 59% of participants.4,7,10,11 To examine the safety an immunogenicity of the vCP1452 Canarypox vector vaccine further, alone and in combination with a protein subunit boost, we undertook a double-blind, randomized, phase 2 study. In this trial, HIV Vaccine Trials Network (HVTN) protocol 203, 4 doses of vCP1452 vaccine were tested at 0, 1, 3, and 6 months alone or in combination with 2 different regimens of rgp120 (3 and 6 months vs. 0, 1, and 6 months). The primary objectives of the trial were to expand the safety profile for these products and to ascertain whether an HIV-specific CD8+ CTL response could be detected at a high enough frequency to qualify the product for subsequent large-scale trials. The trial was co-designed with a test-of-concept efficacy trial that had as its primary objective the definition of a correlate of immunity. Additionally, previous HIV ALVAC vaccine trials relied on a traditional chromium release CTL assay to provide a qualitative assessment of T-cell responses;4,5,7,11,12 this was the first trial to use the interferon-γ (IFNg) enzyme-linked immunospot (ELISpot) assay to measure and quantitate CD8+ CTLs as a primary endpoint.13

  • Comparison of Systemic and Mucosal Delivery of 2 Canarypox Virus Vaccines Expressing either HIV-1 Genes or the Gene for Rabies Virus G Protein
    The Journal of infectious diseases, 2004
    Co-Authors: Peter F. Wright, Paul Spearman, Geoffrey J Gorse, Michael C. Keefer, Jiri Mestecky, M. Juliana Mcelrath, Paul A. Goepfert, Zina Moldoveanu, David H. Schwartz, Raphaelle El Habib
    Abstract:

    Background. Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of Canarypox virus-based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. Methods. Over the course of 6 months, HIV-1-specific (vCP 205) and rabies (vCP 65) Canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. Results. Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1-specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of Canarypox virus vaccine. In contrast, serum IgG rabies and Canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. Conclusions. Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, Canarypox virus was not an effective mucosal immunogen.

  • Safety profile of recombinant Canarypox HIV vaccines
    Vaccine, 2003
    Co-Authors: Guy De Bruyn, Thomas G. Evans, Yalin Chiu, A. J. Rossini, Drienna Holman, Marnie Elizaga, Sharon E. Frey, Donald S. Burke, Lawrence Corey, Michael C. Keefer
    Abstract:

    Attenuated poxviruses have been developed for use as candidate vaccine vectors. ALVAC, a strain of the Avipoxvirus Canarypox, has been extensively evaluated as a vector for vaccines against the human immunodeficiency virus type 1 (HIV-1). This report presents the safety and reactogenicity data derived from 11 multicenter, randomized controlled trials of ALVAC-HIV vaccines conducted by the HIV Vaccine Trials Network (HVTN) and its predecessor, the AIDS Vaccine Evaluation Group (AVEG). Five different ALVAC vaccine constructs were tested among 1497 volunteers. Reactogenicity was similar for different ALVAC constructs. Local reactions of any grade to ALVAC vaccines were common. However, fewer than 2% of vaccinees had severe local responses, and less than 1% experienced severe local pain or tenderness. Systemic responses were mild and transient. As combination vaccine regimens are in common use, we also evaluated side effects of ALVAC vectors given in combination with a recombinant subunit protein. No significant differences were noted in the reactogenicity of ALVAC given with or without a recombinant envelope subunit vaccine. Black, non-Hispanic and male recipients of ALVAC-HIV reported less pain following vaccination than White, non-Hispanics and females, respectively. ALVAC-HIV vaccines are well tolerated at tested doses. The reactogenicity profiles are comparable to those reported for existing vaccines licensed for use among adults. Reactogenicity does not appear to be related to the number or type of inserted genes, and did not vary between different ALVAC constructs.

  • A Canarypox Vaccine Expressing Multiple Human Immunodeficiency Virus Type 1 Genes Given Alone or with Rgp120 Elicits Broad and Durable CD8+ Cytotoxic T Lymphocyte Responses in Seronegative Volunteers
    The Journal of infectious diseases, 1999
    Co-Authors: Thomas G. Evans, Geoffrey J Gorse, Michael C. Keefer, M. Juliana Mcelrath, Kent J. Weinhold, Mark Wolff, David C. Montefiori, Barney S. Graham, Mary Lou Clements-mann, Mark J. Mulligan
    Abstract:

    Induction of CD8 + cytotoxic T cells is considered one of the important correlates for the protective efficacy of candidate human immunodeficiency virus type 1 (HIV-1) vaccines. To induce CD8 + cytotoxic T lymphocytes (CTLs) along with neutralizing antibody and CD4 + T cell help, a live Canarypox virus construct expressing gp120, transmembrane gp41, the gag and protease genes, and sequences containing CTL epitopes in nef and pol was given simultaneously with, or followed by, rgp120 SF2. CD8 + CTLs were detected in 61% of volunteers at some time during the trial. Three to 6 months after the last immunization, the gene-specific responses were gag, 26/81; env, 17/77; nef, 12/77; and pol, 3/16. Simultaneous immunization with the Canarypox vector and the subunit, beginning with the initial immunization, resulted in earlier antibody responses. In summary, a strategy of immunization with a Canarypox vector expressing multiple genes of HIV-1 given with gp120 results in durable CD8 + CTL responses to a broad range of epitopes.

  • 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), 1998
    Co-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 Mcnamara
    Abstract:

    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.