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Dr. Denis Archambault is a faculty member of the Department of Biological Sciences at the University of Québec at Montréal (UQAM) since 1991. He is specialized in RNA viruses (retroviruses, arteriviruses/coronaviruses, influenza virus) and vaccine development. He holds DVM and PhD degrees from University of Montreal. He has completed postdoctoral studies at the prestigious National Institute of Health (NIH) in Bethesda, Maryland (USA), and at the National Laboratory of Immunology in Ottawa (Canada) through fellowships from the Canadian Institutes of Health Research (CIHR) . Then he held a research scholarship from the Fonds de la Recherche en Santé du Québec from 1990 to 2002, while occupying his professor position at UQAM. He also has obtained a MBA degree from Sherbrooke University in 2001. In addition to his commitment in serving on grant review committees and as reviewer for various scientific journals, he has served on the editorial board of "Veterinary Research" from 1994 to 2009). He also has been appointed "Lead Guest Editor" for a special issue on arteriviruses that appeared in March 2014 in the journal "BioMed Research International". His current research work involves studies on new-generation nanovaccine development and virus-host cell interactions. His scientific record shows 94 scientific publications (see Research Scholar and PubMed), 186 presentations at scientific meetings and 80 presentations/seminars, many of them as guest speaker.
Proteinaceous nanostructures have emerged as a promising strategy to develop safe and efficient subunit vaccines. The ability of synthetic β-sheet self-assembling peptides to stabilize antigenic determinants and to potentiate the epitope-specific immune responses have highlighted their potential as an immunostimulating platform for antigen delivery. Nonetheless, the intrinsic polymorphism of the resulting cross-β fibrils, their length in the microscale and their close structural similarity with pathological amyloids could limit their usage in vaccinology. In this study, we harnessed electrostatic capping motifs to control the self-assembly of a chimeric peptide comprising a 10-mer β-sheet sequence and a highly conserved epitope derived from the influenza A virus (M2e). Self-assembly led to the formation of 100–200 nm long uniform nanorods (NRs) displaying the M2e epitope on their surface. These cross-β assemblies differed from prototypical amyloid fibrils owing to low polydispersity, short length, non-binding to thioflavin T and Congo Red dyes, and incapacity to seed homologous amyloid assembly. M2e-NRs were efficiently uptaken by antigen presenting cells and the cross-β quaternary architecture activated the Toll-like receptor 2 and stimulated dendritic cells. Mice subcutaneous immunization revealed a robust M2e-specific IgG response, which was dependent on self-assembly into NRs. Upon intranasal immunization in combination with the polymeric adjuvant montanide gel, M2e-NRs conferred complete protection with absence of clinical signs against a lethal experimental infection with the H1N1 influenza A virus. These findings indicate that by acting as an immunostimulator and delivery system, synthetic peptide-based NRs constitute a versatile self-adjuvanted nanoplatform for the delivery of subunit vaccines.
Ximena Zottigabcd; Soultan Al-Halifa; Mélanie Côté-Cyr; Cynthia Calzase; Ronan Le Goffic; Christophe Chevaliere; Denis Archambaultcd; Steve Bourgaultabd. Self-assembled peptide nanorod vaccine confers protection against influenza A virus. Biomaterials 2021, 269, 120672 .
AMA StyleXimena Zottigabcd, Soultan Al-Halifa, Mélanie Côté-Cyr, Cynthia Calzase, Ronan Le Goffic, Christophe Chevaliere, Denis Archambaultcd, Steve Bourgaultabd. Self-assembled peptide nanorod vaccine confers protection against influenza A virus. Biomaterials. 2021; 269 ():120672.
Chicago/Turabian StyleXimena Zottigabcd; Soultan Al-Halifa; Mélanie Côté-Cyr; Cynthia Calzase; Ronan Le Goffic; Christophe Chevaliere; Denis Archambaultcd; Steve Bourgaultabd. 2021. "Self-assembled peptide nanorod vaccine confers protection against influenza A virus." Biomaterials 269, no. : 120672.
Protein fibrils characterized with a cross-β-sheet quaternary structure have gained interest as nanomaterials in biomedicine, including in the design of subunit vaccines. Recent studies have shown that by conjugating an antigenic determinant to a self-assembling β-peptide, the resulting supramolecular assemblies act as an antigen delivery system that potentiates the epitope-specific immune response. In this study, we used a ten-mer self-assembling sequence (I10) derived from an amyloidogenic peptide to biophysically and immunologically characterize a nanofibril-based vaccine against the influenza virus. The highly conserved epitope from the ectodomain of the matrix protein 2 (M2e) was elongated at the N-terminus of I10 by solid phase peptide synthesis. The chimeric M2e-I10 peptide readily self-assembled into unbranched, long, and twisted fibrils with a diameter between five and eight nm. These cross-β nanoassemblies were cytocompatible and activated the heterodimeric Toll-like receptor (TLR) 2/6. Upon mice subcutaneous immunization, M2e-fibrils triggered a robust anti-M2e specific immune response, which was dependent on self-assembly and did not require the use of an adjuvant. Overall, this study describes the efficacy of cross-β fibrils to activate the TLR 2/6 and to stimulate the epitope-specific immune response, supporting usage of these proteinaceous assemblies as a self-adjuvanted delivery system for antigens.
Soultan Al-Halifa; Ximena Zottig; Margaryta Babych; Mélanie Côté-Cyr; Steve Bourgault; Denis Archambault. Harnessing the Activation of Toll-Like Receptor 2/6 by Self-Assembled Cross-β Fibrils to Design Adjuvanted Nanovaccines. Nanomaterials 2020, 10, 1981 .
AMA StyleSoultan Al-Halifa, Ximena Zottig, Margaryta Babych, Mélanie Côté-Cyr, Steve Bourgault, Denis Archambault. Harnessing the Activation of Toll-Like Receptor 2/6 by Self-Assembled Cross-β Fibrils to Design Adjuvanted Nanovaccines. Nanomaterials. 2020; 10 (10):1981.
Chicago/Turabian StyleSoultan Al-Halifa; Ximena Zottig; Margaryta Babych; Mélanie Côté-Cyr; Steve Bourgault; Denis Archambault. 2020. "Harnessing the Activation of Toll-Like Receptor 2/6 by Self-Assembled Cross-β Fibrils to Design Adjuvanted Nanovaccines." Nanomaterials 10, no. 10: 1981.
Lentivirus genomes code for a regulatory protein essential for virus replication termed Rev. The Rev protein binds to partially spliced and unspliced viral RNAs and mediates their nuclear export. Therefore, Rev possesses functional domains that enable its shuttling between the cytoplasm and the nucleus. The Feline immunodeficiency virus (FIV), a lentivirus, can lead to an immunodeficiency syndrome after a long incubation period, similar to that associated with the human immunodeficiency virus type 1 (HIV-1). The FIV Rev functional domains have been predicted only by homology with those of HIV-1 Rev. In the present study, the nuclear and nucleolar localization signals (NLS and NoLS, respectively) of the FIV Rev were examined. A series of FIV Rev deletion mutants fused to the enhanced green fluorescent protein (EGFP) were used to localize the NLS in a region spanning amino acids (aa) 81–100. By using alanine substitution mutants, basic residues present between the amino acids (aa) 84–99 of the FIV Rev protein sequence were identified to form the NLS, whereas those between aa 82–95 were associated with the NoLS function. These results further enhance our understanding of how Rev exerts its role in the replication cycle of lentiviruses.
Claude Marchand; Guy Lemay; Denis Archambault. Identification of the nuclear and nucleolar localization signals of the Feline immunodeficiency virus Rev protein. Virus Research 2020, 290, 198153 .
AMA StyleClaude Marchand, Guy Lemay, Denis Archambault. Identification of the nuclear and nucleolar localization signals of the Feline immunodeficiency virus Rev protein. Virus Research. 2020; 290 ():198153.
Chicago/Turabian StyleClaude Marchand; Guy Lemay; Denis Archambault. 2020. "Identification of the nuclear and nucleolar localization signals of the Feline immunodeficiency virus Rev protein." Virus Research 290, no. : 198153.
Caprine arthritis-encephalitis virus (CAEV), a lentivirus, relies on the action of the Rev protein for its replication. The CAEV Rev fulfills its function by allowing the nuclear exportation of partially spliced or unspliced viral mRNAs. In this study, we characterized the nuclear and nucleolar localization signals (NLS and NoLS, respectively) and the nuclear export signal (NES) of the CAEV Rev protein. These signals are key actors in the nucleocytoplasmic shuttling of a lentiviral Rev protein. Several deletion and alanine substitution mutants were generated from a plasmid encoding the CAEV Rev wild-type protein that was fused to the enhanced green fluorescent protein (EGFP). Following cell transfection, images were captured by confocal microscopy and the fluorescence was quantified in the different cell compartments. The results showed that the NLS region is localized between amino acids (aa) 59 to 75, has a monopartite-like structure and is exclusively composed of arginine residues. The NoLS was found to be partially associated with the NLS. Finally, the CAEV Rev protein’s NES mapped between aa 89 to 101, with an aa spacing between the hydrophobic residues that was found to be unconventional as compared to that of other retroviral Rev/Rev-like proteins.
Marlène Labrecque; Claude Marchand; Denis Archambault. Characterization of Signal Sequences Determining the Nuclear/Nucleolar Import and Nuclear Export of the Caprine Arthritis-Encephalitis Virus Rev Protein. Viruses 2020, 12, 900 .
AMA StyleMarlène Labrecque, Claude Marchand, Denis Archambault. Characterization of Signal Sequences Determining the Nuclear/Nucleolar Import and Nuclear Export of the Caprine Arthritis-Encephalitis Virus Rev Protein. Viruses. 2020; 12 (8):900.
Chicago/Turabian StyleMarlène Labrecque; Claude Marchand; Denis Archambault. 2020. "Characterization of Signal Sequences Determining the Nuclear/Nucleolar Import and Nuclear Export of the Caprine Arthritis-Encephalitis Virus Rev Protein." Viruses 12, no. 8: 900.
Life-inspired protein supramolecular assemblies have recently attracted considerable attention for the development of next-generation vaccines to fight against infectious diseases, as well as autoimmune diseases and cancer. Protein self-assembly enables atomic scale precision over the final architecture, with a remarkable diversity of structures and functionalities. Self-assembling protein nanovaccines are associated with numerous advantages, including biocompatibility, stability, molecular specificity and multivalency. Owing to their nanoscale size, proteinaceous nature, symmetrical organization and repetitive antigen display, protein assemblies closely mimic most invading pathogens, serving as danger signals for the immune system. Elucidating how the structural and physicochemical properties of the assemblies modulate the potency and the polarization of the immune responses is critical for bottom-up design of vaccines. In this context, this review briefly covers the fundamentals of supramolecular interactions involved in protein self-assembly and presents the strategies to design and functionalize these assemblies. Examples of advanced nanovaccines are presented, and properties of protein supramolecular structures enabling modulation of the immune responses are discussed. Combining the understanding of the self-assembly process at the molecular level with knowledge regarding the activation of the innate and adaptive immune responses will support the design of safe and effective nanovaccines.
Ximena Zottig; Mélanie Côté-Cyr; Dominic Arpin; Denis Archambault; Steve Bourgault. Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design. Nanomaterials 2020, 10, 1008 .
AMA StyleXimena Zottig, Mélanie Côté-Cyr, Dominic Arpin, Denis Archambault, Steve Bourgault. Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design. Nanomaterials. 2020; 10 (5):1008.
Chicago/Turabian StyleXimena Zottig; Mélanie Côté-Cyr; Dominic Arpin; Denis Archambault; Steve Bourgault. 2020. "Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design." Nanomaterials 10, no. 5: 1008.
By modulating specific immune responses against antigens, adjuvants are used in many vaccine preparations to enhance protective immunity. The C-terminal domain of the protein P97 (P97c) of Mycoplasma hyopneumoniae, which is the etiologic agent of porcine enzootic pneumonia, has been shown to increase the specific humoral response against an antigen when this antigen is merged with P97c and delivered by adenovectors. However, the immunostimulating mechanism of this protein remains unknown. In the present study, recombinantly expressed P97c triggered a concentration-dependent TLR5 activation and stimulates the production of interleukin-8 from HEK-Blue mTLR5 cells. Circular dichroism spectroscopy and prediction of 3-dimensional conformation exposed a relevant secondary and tertiary structural homology between P97c and flagellin, the known potent TLR5 agonist. P97c adjuvanticity was evaluated by fusing the conserved epitope of the ectodomain matrix 2 protein (M2e) of the influenza A virus to the protein. Mice immunized with P97c-3M2e revealed a high antibody titer against the M2e epitope associated with a mixed Th1/Th2 immune response. Overall, this study identifies a novel agonist of the pattern recognition receptor TLR5 and reveals that P97c is a potential adjuvant through the activation of the innate immune system.
Laurie Gauthier; Margaryta Babych; Mariela Segura; Steve Bourgault; Denis Archambault. Identification of a novel TLR5 agonist derived from the P97 protein of Mycoplasma hyopneumoniae. Immunobiology 2020, 225, 151962 .
AMA StyleLaurie Gauthier, Margaryta Babych, Mariela Segura, Steve Bourgault, Denis Archambault. Identification of a novel TLR5 agonist derived from the P97 protein of Mycoplasma hyopneumoniae. Immunobiology. 2020; 225 (4):151962.
Chicago/Turabian StyleLaurie Gauthier; Margaryta Babych; Mariela Segura; Steve Bourgault; Denis Archambault. 2020. "Identification of a novel TLR5 agonist derived from the P97 protein of Mycoplasma hyopneumoniae." Immunobiology 225, no. 4: 151962.
The lentiviral Rev protein, which is a regulatory protein essential for virus replication, has been first studied in the human immunodeficiency virus type 1 (HIV-1). The main function of Rev is to mediate the nuclear exportation of viral RNAs. To fulfill its function, Rev shuttles between the cytoplasm and the nucleus. The Jembrana disease virus (JDV), a lentivirus, is the etiologic agent of the Jembrana disease which was first described in Bali cattle in Indonesia in 1964. Despite the high mortality rate associated with JDV, this virus remains poorly studied. Herein the subcellular distribution of JDV Rev, the nuclear and nucleolar localization signals (NLS and NoLS, respectively) and the nuclear export signal (NES) of the protein were examined. JDV Rev fused to the enhanced green fluorescent protein (EGFP) predominantly localized to the cytoplasm and nucleolus of transfected cells, as determined by fluorescence microscopy analyses. Through transfection of a series of deletion mutants of JDV Rev, it was possible to localize the NLS/NoLS region between amino acids (aa) 74 to 105. By substituting basic residues with alanine within this sequence, we demonstrated that the JDV Rev NLS encompasses aa 76 to 86, and is exclusively composed of arginine residues, whereas a bipartite NoLS was observed for the first time in any retroviral Rev/Rev-like proteins. Finally, a NES was identified downstream of the NLS/NoLS and encompasses aa 116 to 128 of the JDV Rev protein. The JDV Rev NES was found to be of the protein kinase A inhibitor (PKI) class instead of the HIV-1 Rev class. It also corresponds to the most optimal consensus sequence of PKI NES and, as such, is novel among lentiviral Rev NES.
Claude Marchand; Guy Lemay; Denis Archambault. The Jembrana disease virus Rev protein: Identification of nuclear and novel lentiviral nucleolar localization and nuclear export signals. PLOS ONE 2019, 14, e0221505 .
AMA StyleClaude Marchand, Guy Lemay, Denis Archambault. The Jembrana disease virus Rev protein: Identification of nuclear and novel lentiviral nucleolar localization and nuclear export signals. PLOS ONE. 2019; 14 (8):e0221505.
Chicago/Turabian StyleClaude Marchand; Guy Lemay; Denis Archambault. 2019. "The Jembrana disease virus Rev protein: Identification of nuclear and novel lentiviral nucleolar localization and nuclear export signals." PLOS ONE 14, no. 8: e0221505.
The respiratory mucosa is the primary portal of entry for numerous viruses such as the respiratory syncytial virus, the influenza virus and the parainfluenza virus. These pathogens initially infect the upper respiratory tract and then reach the lower respiratory tract, leading to diseases. Vaccination is an affordable way to control the pathogenicity of viruses and constitutes the strategy of choice to fight against infections, including those leading to pulmonary diseases. Conventional vaccines based on live-attenuated pathogens present a risk of reversion to pathogenic virulence while inactivated pathogen vaccines often lead to a weak immune response. Subunit vaccines were developed to overcome these issues. However, these vaccines may suffer from a limited immunogenicity and, in most cases, the protection induced is only partial. A new generation of vaccines based on nanoparticles has shown great potential to address most of the limitations of conventional and subunit vaccines. This is due to recent advances in chemical and biological engineering, which allow the design of nanoparticles with a precise control over the size, shape, functionality and surface properties, leading to enhanced antigen presentation and strong immunogenicity. This short review provides an overview of the advantages associated with the use of nanoparticles as vaccine delivery platforms to immunize against respiratory viruses and highlights relevant examples demonstrating their potential as safe, effective and affordable vaccines.
Soultan Al-Halifa; Laurie Gauthier; Dominic Arpin; Steve Bourgault; Denis Archambault. Nanoparticle-Based Vaccines Against Respiratory Viruses. Frontiers in Immunology 2019, 10, 22 .
AMA StyleSoultan Al-Halifa, Laurie Gauthier, Dominic Arpin, Steve Bourgault, Denis Archambault. Nanoparticle-Based Vaccines Against Respiratory Viruses. Frontiers in Immunology. 2019; 10 ():22.
Chicago/Turabian StyleSoultan Al-Halifa; Laurie Gauthier; Dominic Arpin; Steve Bourgault; Denis Archambault. 2019. "Nanoparticle-Based Vaccines Against Respiratory Viruses." Frontiers in Immunology 10, no. : 22.
The bovine immunodeficiency virus (BIV) Rev shuttling protein contains nuclear/nucleolar localization signals and nuclear import/export mechanisms that are novel among lentivirus Rev proteins. Several viral proteins localize to the nucleolus, which may play a role in processes that are essential to the outcome of viral replication. Although BIV Rev localizes to the nucleoli of transfected/infected cells and colocalizes with one of its major proteins, nucleophosmin (NPM1, also known as B23), the role of the nucleolus and B23 in BIV replication remains to be determined. Here, we demonstrate for the first time that BIV Rev interacts with nucleolar phosphoprotein B23 in cells. Using small interfering RNA (siRNA) technology, we show that depletion of B23 expression inhibits virus production by BIV-infected cells, indicating that B23 plays an important role in BIV replication. The interaction between Rev and B23 may represent a potential new target for the development of antiviral drugs against lentiviruses.
Ana Maria Passos-Castilho; Claude Marchand; Denis Archambault. B23/nucleophosmin interacts with bovine immunodeficiency virus Rev protein and facilitates viral replication. Virology 2018, 515, 158 -164.
AMA StyleAna Maria Passos-Castilho, Claude Marchand, Denis Archambault. B23/nucleophosmin interacts with bovine immunodeficiency virus Rev protein and facilitates viral replication. Virology. 2018; 515 ():158-164.
Chicago/Turabian StyleAna Maria Passos-Castilho; Claude Marchand; Denis Archambault. 2018. "B23/nucleophosmin interacts with bovine immunodeficiency virus Rev protein and facilitates viral replication." Virology 515, no. : 158-164.
Denis Archambault. Localization of the RNA Binding Domain of the IHi Bovine Immunodeficiency Virus Rev Protein. Advances in Biotechnology & Microbiology 2017, 5, 1 .
AMA StyleDenis Archambault. Localization of the RNA Binding Domain of the IHi Bovine Immunodeficiency Virus Rev Protein. Advances in Biotechnology & Microbiology. 2017; 5 (3):1.
Chicago/Turabian StyleDenis Archambault. 2017. "Localization of the RNA Binding Domain of the IHi Bovine Immunodeficiency Virus Rev Protein." Advances in Biotechnology & Microbiology 5, no. 3: 1.
The porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus of the Arteriviridae family. As the current commercial vaccines are incompletely protective effective against PRRSV infection, we developed a vaccine strategy using replicating but non-disseminating adenovectors (rAdVs) expressing the PRRSV M matrix protein in fusion with the neutralizing major epitope-carrying GP5 envelope protein (Roques et al. in Vet Res 44:17, 2013). Although production of GP5-specific antibodies (Abs) was observed, no PRRSV-specific neutralizing Abs (NAbs) were induced in pigs given the rAdVs expressing M-GP5 or M-GP5m (GP5m being a mutant form of GP5). Nevertheless, partial protection was observed in the M-GP5m-rAdV-inoculated pigs experimentally infected with PRRSV. Here, we determined the impact of the cholera toxin B subunit (CTB, known for its adjuvant effect) in fusion with the C-terminus of M-GP5m on the Ab response to PRRSV. Three-week-old pigs were immunized twice both intramuscularly and intranasally at 3-week intervals with rAdV-expressing the green fluorescent protein (rAdV-GFP), rAdV-M-GP5m, or rAdV-M-GP5m-CTB. Pigs immunized with rAdV-M-GP5m showed a high level of serum GP5-specific Abs (as determined by an indirect ELISA). In contrast, CTB in fusion with M-GP5m had an unexpected severe negative impact on GP5-specific Ab production. PRRSV-specific NAbs could not be detected in any pigs of all groups.
Elodie Roques; Martin Lessard; Denis Archambault. The Cholera Toxin B Subunit (CTB) Fused to the Porcine Arterivirus Matrix M and GP5 Envelope Proteins Fails to Enhance the GP5-Specific Antibody Response in Pigs Immunized with Adenovectors. Molecular Biotechnology 2015, 57, 701 -708.
AMA StyleElodie Roques, Martin Lessard, Denis Archambault. The Cholera Toxin B Subunit (CTB) Fused to the Porcine Arterivirus Matrix M and GP5 Envelope Proteins Fails to Enhance the GP5-Specific Antibody Response in Pigs Immunized with Adenovectors. Molecular Biotechnology. 2015; 57 (8):701-708.
Chicago/Turabian StyleElodie Roques; Martin Lessard; Denis Archambault. 2015. "The Cholera Toxin B Subunit (CTB) Fused to the Porcine Arterivirus Matrix M and GP5 Envelope Proteins Fails to Enhance the GP5-Specific Antibody Response in Pigs Immunized with Adenovectors." Molecular Biotechnology 57, no. 8: 701-708.
Denis Archambault; Udeni B. R. Balasuriya; Raymond R. R. Rowland; Hanchun Yang; Dongwan Yoo. Animal Arterivirus Infections. BioMed Research International 2014, 2014, 1 -2.
AMA StyleDenis Archambault, Udeni B. R. Balasuriya, Raymond R. R. Rowland, Hanchun Yang, Dongwan Yoo. Animal Arterivirus Infections. BioMed Research International. 2014; 2014 ():1-2.
Chicago/Turabian StyleDenis Archambault; Udeni B. R. Balasuriya; Raymond R. R. Rowland; Hanchun Yang; Dongwan Yoo. 2014. "Animal Arterivirus Infections." BioMed Research International 2014, no. : 1-2.
Human rotavirus (HRV) is the worldwide leading cause of gastroenteritis in young children. Two live attenuated HRV vaccines have been approved since 2006. However, these live vaccines still have potential risks including reversion of virulence. Adenoviruses are suitable vectors for mucosal administration of subunit vaccines. In addition to the adjuvant effect of certain adenovirus components, the use of an adjuvant like flagellin is also another means to increase the immune response to the immunogen. The aim of this study was to determine whether flagellin in fusion with HRV structural proteins stimulates the innate immune response and enhances the HRV-specific immune response when delivered through the intrarectal route with replicating but non-disseminating adenovector (R-AdV). Salmonella typhimurium flagellin B (FljB) in fusion with HRV VP4Δ::VP7 protein induced IL-1β production in J774A.1 macrophages exposed to the R-AdV. Intrarectal administration of R-AdVs expressing either VP4Δ::VP7 or VP4Δ::VP7::FljB in BALB/c mice resulted in HRV-specific mixed Th1/Th2 immune responses. The HRV-specific antibody response elicited with the use of R-AdV expressing VP4Δ::VP7::FljB was higher than that with R-AdV expressing VP4Δ::VP7. The results also show that the replication capability of R-AdVs contributed to enhance the HRV-specific immune response as compared with that obtained with non-replicative AdVs. This work lays the foundation for using the R-AdV system and FljB-adjuvanted formulation to elicit a mucosal immune response specific to HRV.
Aurélie Girard; Elodie Roques; Bernard Massie; Denis Archambault. Flagellin in Fusion with Human Rotavirus Structural Proteins Exerts an Adjuvant Effect When Delivered with Replicating but Non-Disseminating Adenovectors Through the Intrarectal Route. Molecular Biotechnology 2013, 56, 394 -407.
AMA StyleAurélie Girard, Elodie Roques, Bernard Massie, Denis Archambault. Flagellin in Fusion with Human Rotavirus Structural Proteins Exerts an Adjuvant Effect When Delivered with Replicating but Non-Disseminating Adenovectors Through the Intrarectal Route. Molecular Biotechnology. 2013; 56 (5):394-407.
Chicago/Turabian StyleAurélie Girard; Elodie Roques; Bernard Massie; Denis Archambault. 2013. "Flagellin in Fusion with Human Rotavirus Structural Proteins Exerts an Adjuvant Effect When Delivered with Replicating but Non-Disseminating Adenovectors Through the Intrarectal Route." Molecular Biotechnology 56, no. 5: 394-407.
Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine Circovirus type 2 (PCV2) and Mycoplasma (M.) hyopneumoniae are swine pathogens of economic importance. Although vaccines are available for each pathogen, no commercial bivalent vaccines have been developed so far. In this study, recombinant adenovectors (AdVs) expressing proteins of each pathogen were developed and their immunogenicity tested in mice. The proteins of interest were the glycoprotein GP5 of PRRSV, the capsid (Cap) protein of PCV2b and the C-terminal portion of P97 (P97c) protein of M. hyopneumoniae that were used alone and/or in fusion which each other. Inoculation of mice with the AdVs resulted in antibody (Ab) responses specific to the immunogens. Unexpectedly, immunization with vaccines expressing P97c in fusion to either Cap or GP5 enhanced the Ab responses against Cap and GP5, suggesting an immunopotentiator effect for P97c.
Elodie Roques; Aurélie Girard; Carl A. Gagnon; Denis Archambault. Antibody responses induced in mice immunized with recombinant adenovectors expressing chimeric proteins of various porcine pathogens. Vaccine 2013, 31, 2698 -2704.
AMA StyleElodie Roques, Aurélie Girard, Carl A. Gagnon, Denis Archambault. Antibody responses induced in mice immunized with recombinant adenovectors expressing chimeric proteins of various porcine pathogens. Vaccine. 2013; 31 (24):2698-2704.
Chicago/Turabian StyleElodie Roques; Aurélie Girard; Carl A. Gagnon; Denis Archambault. 2013. "Antibody responses induced in mice immunized with recombinant adenovectors expressing chimeric proteins of various porcine pathogens." Vaccine 31, no. 24: 2698-2704.
The aim of this study was to evaluate the usefulness of replicating but non disseminating adenovirus vectors (AdVs) as vaccine vector using human rotavirus (HRV) as a model pathogen. HRV VP7, VP4, or VP4Δ (N-terminal 336 amino acids of VP4) structural proteins as well as the VP4Δ::VP7 chimeric fusion protein were expressed in mammalian cells when delivered with the AdVs. A preliminary experiment demonstrated that VP4Δ was able to induce a HRV-specific IgG response in BALB/c mice inoculated intramuscularly with AdVs expressing the rotaviral protein. Moreover, an AdV-prime/plasmid DNA-boost regimen of vectors resulted in VP4Δ-specific antibody (Ab) titers ~4 times higher than those obtained from mice immunized with AdVs alone. Subsequently, the various HRV protein-encoding AdVs were compared using the AdV-prime/plasmid DNA-boost regimen. Higher IgG and IgA responses to HRV were obtained when VP4Δ::VP7 fusion protein was used as an immunogen as compared to VP7 or VP4 alone or to a mix of both proteins delivered independently by AdVs. A synergetic effect in terms of Ab was obtained with VP4Δ::VP7. In conclusion, this study demonstrated for the first time the suitability of using replicating but non disseminating AdVs as vaccine vector and the VP4Δ::VP7 fusion protein as an immunogen for vaccination against HRV.
Aurélie Girard; Elodie Roques; Marie-Claude St-Louis; Bernard Massie; Denis Archambault. Expression of Human Rotavirus Chimeric Fusion Proteins from Replicating but Non Disseminating Adenovectors and Elicitation of Rotavirus-Specific Immune Responses in Mice. Molecular Biotechnology 2013, 54, 1010 -1020.
AMA StyleAurélie Girard, Elodie Roques, Marie-Claude St-Louis, Bernard Massie, Denis Archambault. Expression of Human Rotavirus Chimeric Fusion Proteins from Replicating but Non Disseminating Adenovectors and Elicitation of Rotavirus-Specific Immune Responses in Mice. Molecular Biotechnology. 2013; 54 (3):1010-1020.
Chicago/Turabian StyleAurélie Girard; Elodie Roques; Marie-Claude St-Louis; Bernard Massie; Denis Archambault. 2013. "Expression of Human Rotavirus Chimeric Fusion Proteins from Replicating but Non Disseminating Adenovectors and Elicitation of Rotavirus-Specific Immune Responses in Mice." Molecular Biotechnology 54, no. 3: 1010-1020.
Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for significant economic losses in the porcine industry. Currently available commercial vaccines do not allow optimal and safe protection. In this study, replicating but nondisseminating adenovectors (rAdV) were used for the first time in pigs for vaccinal purposes. They were expressing the PRRSV matrix M protein in fusion with either the envelope GP5 wild-type protein (M-GP5) which carries the major neutralizing antibody (NAb)-inducing epitope or a mutant form of GP5 (M-GP5m) developed to theoretically increase the NAb immune response. Three groups of fourteen piglets were immunized both intramuscularly and intranasally at 3-week intervals with rAdV expressing the green fluorescent protein (GFP, used as a negative control), M-GP5 or M-GP5m. Two additional groups of pigs were primed with M-GP5m-expressing rAdV followed by a boost with bacterially-expressed recombinant wild-type GP5 or were immunized twice with a PRRSV inactivated commercial vaccine. The results show that the rAdV expressing the fusion proteins of interest induced systemic and mucosal PRRSV GP5-specific antibody response as determined in an ELISA. Moreover the prime with M-GP5m-expressing rAdV and boost with recombinant GP5 showed the highest antibody response against GP5. Following PRRSV experimental challenge, pigs immunized twice with rAdV expressing either M-GP5 or M-GP5m developed partial protection as shown by a decrease in viremia overtime. The lowest viremia levels and/or percentages of macroscopic lung lesions were obtained in pigs immunized twice with either the rAdV expressing M-GP5m or the PRRSV inactivated commercial vaccine.
Elodie Roques; Aurélie Girard; Marie-Claude St-Louis; Bernard Massie; Carl A Gagnon; Martin Lessard; Denis Archambault. Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors. Veterinary Research 2013, 44, 17 -17.
AMA StyleElodie Roques, Aurélie Girard, Marie-Claude St-Louis, Bernard Massie, Carl A Gagnon, Martin Lessard, Denis Archambault. Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors. Veterinary Research. 2013; 44 (1):17-17.
Chicago/Turabian StyleElodie Roques; Aurélie Girard; Marie-Claude St-Louis; Bernard Massie; Carl A Gagnon; Martin Lessard; Denis Archambault. 2013. "Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors." Veterinary Research 44, no. 1: 17-17.
The Rev protein is essential for the replication of lentiviruses. Rev is a shuttling protein that transports unspliced and partially spliced lentiviral RNAs from the nucleus to the cytoplasm via the nucleopore. To transport these RNAs, the human immunodeficiency virus type 1 (HIV-1) Rev uses the karyopherin β family importin β and CRM1 proteins that interact with the Rev nuclear localization signal (NLS) and nuclear exportation signal (NES), respectively. Recently, we reported the presence of new types of bipartite NLS and nucleolar localization signal (NoLS) in the bovine immunodeficiency virus (BIV) Rev protein. Here we report the characterization of the nuclear import and export pathways of BIV Rev. By using an in vitro nuclear import assay, we showed that BIV Rev is transported into the nucleus by a cytosolic and energy-dependent importin α/β classical pathway. Results from glutathione S-transferase (GST) pulldown assays that showed the binding of BIV Rev with importins α3 and α5 were in agreement with those from the nuclear import assay. We also identified a leptomycin B-sensitive NES in BIV Rev, which indicates that the protein is exported via CRM1 like HIV-1 Rev. Mutagenesis experiments showed that the BIV Rev NES maps between amino acids 109 to 121 of the protein. Remarkably, the BIV Rev NES was found to be of the cyclic AMP (cAMP)-dependent protein kinase inhibitor (PKI) type instead of the HIV-1 Rev type. In summary, our data showed that the nuclear import mechanism of BIV Rev is novel among Rev proteins characterized so far in lentiviruses.
Andrea Gomez Corredor; Denis Archambault. The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Nuclear Import Pathway and Nuclear Export Signal among Retroviral Rev/Rev-Like Proteins. Journal of Virology 2012, 86, 4892 -4905.
AMA StyleAndrea Gomez Corredor, Denis Archambault. The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Nuclear Import Pathway and Nuclear Export Signal among Retroviral Rev/Rev-Like Proteins. Journal of Virology. 2012; 86 (9):4892-4905.
Chicago/Turabian StyleAndrea Gomez Corredor; Denis Archambault. 2012. "The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Nuclear Import Pathway and Nuclear Export Signal among Retroviral Rev/Rev-Like Proteins." Journal of Virology 86, no. 9: 4892-4905.
The aim of this study was to produce adjuvant with high biosafety, efficacy and low cost. Towards this goal, the plant Nicotiana benthamiana transient expression system was successfully used to express Salmonella typhimurium's flagellin (FljB). The yield of the expressed FljB was 280 mg per kg of fresh weight (FW) leaves. The lyophilized plant powder containing plant expressing FljB was mixed with ovalbumin (OVA) and used for oral immunization of BALB/c mice. The ELISA analysis showed higher and accelerated OVA-specific serum antibody responses in mice given the mixture when compared to animals receiving OVA alone. Furthermore, FljB elicited a mixed Th1/Th2 response as shown by the presence of specific anti-OVA IgG1, IgG2a and IgG2b isotypes. OVA-specific IgAs were also detected in mice given the mixture. Cell-mediated immune response to OVA was induced by FljB as determined by a spleen lymphocyte specific proliferation test. No immune response was generated against FljB. In conclusion, our results showed for the first time the production of FljB in plants and the efficient use of the crude lyophilized extract as an adjuvant for oral immunization.
Aurélie Girard; Wilfried Saron; Louis-Philippe Bergeron-Sandoval; Fathey Sarhan; Denis Archambault. Flagellin produced in plants is a potent adjuvant for oral immunization. Vaccine 2011, 29, 6695 -6703.
AMA StyleAurélie Girard, Wilfried Saron, Louis-Philippe Bergeron-Sandoval, Fathey Sarhan, Denis Archambault. Flagellin produced in plants is a potent adjuvant for oral immunization. Vaccine. 2011; 29 (38):6695-6703.
Chicago/Turabian StyleAurélie Girard; Wilfried Saron; Louis-Philippe Bergeron-Sandoval; Fathey Sarhan; Denis Archambault. 2011. "Flagellin produced in plants is a potent adjuvant for oral immunization." Vaccine 29, no. 38: 6695-6703.
The bovine immunodeficiency virus (BIV) Rev protein (186 amino acids [aa] in length) is involved in the nuclear exportation of partially spliced and unspliced viral RNAs. Previous studies have shown that BIV Rev localizes in the nucleus and nucleolus of infected cells. Here we report the characterization of the nuclear/nucleolar localization signals (NLS/NoLS) of this protein. Through transfection of a series of deletion mutants of BIV Rev fused to enhanced green fluorescent protein and fluorescence microscopy analyses, we were able to map the NLS region between aa 71 and 110 of the protein. Remarkably, by conducting alanine substitution of basic residues within the aa 71 to 110 sequence, we demonstrated that the BIV Rev NLS is bipartite, maps to aa 71 to 74 and 95 to 101, and is predominantly composed of arginine residues. This is the first report of a bipartite Rev (or Rev-like) NLS in a lentivirus/retrovirus. Moreover, this NLS is atypical, as the length of the sequence between the motifs composing the bipartite NLS, e.g., the spacer sequence, is 20 aa. Further mutagenesis experiments also identified the NoLS region of BIV Rev. It localizes mainly within the NLS spacer sequence. In addition, the BIV Rev NoLS sequence differs from the consensus sequence reported for other viral and cellular nucleolar proteins. In summary, we conclude that the nucleolar and nuclear localizations of BIV Rev are mediated via novel NLS and NoLS motifs.
Andrea Gomez Corredor; Denis Archambault. The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Lentiviral Bipartite Nuclear Localization Signal Harboring an Atypical Spacer Sequence. Journal of Virology 2009, 83, 12842 -12853.
AMA StyleAndrea Gomez Corredor, Denis Archambault. The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Lentiviral Bipartite Nuclear Localization Signal Harboring an Atypical Spacer Sequence. Journal of Virology. 2009; 83 (24):12842-12853.
Chicago/Turabian StyleAndrea Gomez Corredor; Denis Archambault. 2009. "The Bovine Immunodeficiency Virus Rev Protein: Identification of a Novel Lentiviral Bipartite Nuclear Localization Signal Harboring an Atypical Spacer Sequence." Journal of Virology 83, no. 24: 12842-12853.
We previously identified a new bovine immunodeficiency virus (BIV) trans-activator factor of transcription (Tat236) that was derived from a variant of BIV. Here, we report a new BIV long terminal repeat (LTR) sequence (LTRn) that was obtained by PCR from the DNA of cells infected with the BIV variant mentioned above. Sequence analysis indicated that the LTRn U3 region harbors three nucleic acid mutations at residue positions −194, −135 and −114 when compared to the original (wild-type) LTR sequence. Reporter gene assays indicated that LTRn promotes basal and Tat-mediated transactivation activity to levels significantly higher than those obtained with the wild-type LTR. Restoration experiments to the wild-type genotype indicated that both the −135 and −114 nucleic acid substitutions were responsible for the enhanced promoter activity of BIV LTRn.
M. Cojocariu; M.-C. St-Louis; D. Archambault. Bovine immunodeficiency virus: identification of a long terminal repeat sequence with enhanced promoter activity. Archives of Virology 2009, 154, 1163 -1167.
AMA StyleM. Cojocariu, M.-C. St-Louis, D. Archambault. Bovine immunodeficiency virus: identification of a long terminal repeat sequence with enhanced promoter activity. Archives of Virology. 2009; 154 (7):1163-1167.
Chicago/Turabian StyleM. Cojocariu; M.-C. St-Louis; D. Archambault. 2009. "Bovine immunodeficiency virus: identification of a long terminal repeat sequence with enhanced promoter activity." Archives of Virology 154, no. 7: 1163-1167.