VIDO-InterVac
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The Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) is a world leader in infectious disease research and vaccine development. With more than 150 personnel and over four decades of experience, the organization performs research on diseases that impact human and animal health. VIDO-InterVac is a research organization of the University of Saskatchewan and has some of the most advanced containment Level 2 and 3 facilities in the world.
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Item Combination therapy enhances the antiviral activity of IFN-λ against SARS-CoV-2 and MERS-CoV(Elsevier, 2025-03) Rajabali Zadeh, Vahid; Lew, Jocelyne M.; Zahoor, Muhammad Atif; Santer, Deanna; Feld, Jordan J.; Falzarano, DarrylTherapeutic options against pathogenic human coronaviruses remain limited. In a recent clinical trial, we demonstrated the therapeutic efficacy of pegylated-IFN-λ in COVID-19 outpatients. However, the emergence of variants that have the potential to evade IFN-mediated antiviral responses raises concerns regarding the continued efficacy of this approach. In this work, we compared the sensitivity of SARS-CoV-2 variants and MERS-CoV to IFN-λ treatment in vitro and explored the potential of combination therapy with other FDA-authorized or approved antiviral agents. We observed that in contrast to the ancestral strain, all other SARS-CoV-2 lineages showed varying, but increased resistance to IFN-λ treatment, from a 5.7-fold increase in EC50 value for the P.1 strain to a 32.7-fold increase for the B.1.1.7 variant. We further show that combination treatment with remdesivir or nirmatrelvir enhanced the antiviral effect of IFN-λ against both SARS-CoV-2 and MERS-CoV. These findings justify the initiation of further in vivo testing that ultimately can help inform the development of more effective therapeutic guidelines against pathogenic coronaviruses.Item Combined immunoinformatic approaches with computational biochemistry for development of subunit-based vaccine against Lawsonia intracellularis(PLoS One, 2025-02) Khatooni, Zahed; Broderick, Gordon; Anand, Sanjeev K.; Wilson, HeatherLawsonia intracellularis (LI) are obligate intracellular bacteria and the causative agent of proliferative hemorrhagic enteropathy that significantly impacts the health of piglets and the profitability of the swine industry. In this study, we used immunoinformatic and computational methodologies such as homology modelling, molecular docking, molecular dynamic (MD) simulation, and free energy calculations in a novel three stage approach to identify strong T and B cell epitopes in the LI proteome. From ∼ 1342 LI proteins, we narrowed our focus to 256 proteins that were either not well-identified (unknown role) or were expressed at a higher frequency in pathogenic strains relative to non-pathogenic strains. At stage 1, these proteins were analyzed for predicted virulence, antigenicity, solubility, and probability of residing within a membrane. At stage 2, we used NetMHCPan4-1 to identify over ten thousand cytotoxic T lymphocyte epitopes (CTLEs) and 286 CTLEs were ranked as having high predicted binding affinity for the SLA-1 and SLA-2 complexes. At stage 3, we used homology modeling to predict the structures of the top ranked CTLEs and we subjected each of them to molecular docking analysis with SLA-1*0401 and SLA-2*0402. The top ranked 25 SLA–CTLE complexes were selected to be an input for subsequent MD simulations to fully investigate the atomic-level dynamics of proteins under the natural thermal fluctuation of water and thus potentially provide deep insight into the CTLE-SLA interaction. We also performed free energy evaluation by Molecular Mechanics/Poisson−Boltzmann Surface Area to predict epitope interactions and binding affinities to the SLA-1 and SLA-2. We identified the top five CTLEs having the strongest binding energy to the indicated SLAs (-305.6 kJ/mol, -219.5 kJ/mol, -214.8 kJ/mol, -139.5 kJ/mol and -92.6 kJ/mol, respectively.) W also performed B-cell epitope prediction and the top-ranked 5 CTLEs and 3 B-cell epitopes were organized into a multi-epitope subunit antigen vaccine construct joined using EAAAK, AAY, KK, and GGGGG linkers with 40 residues of the LI DnaK protein attached to the N-terminus to further enhance the antigenicity of the vaccine construct. Blind docking studies showed strong interactions between our vaccine construct with swine Toll-like receptor 5. Collectively, these molecular modeling and immunoinformatic analyses present a useful in silico protocol for the discovery of candidate antigen in many viral and bacterial pathogens.Item Towards developing multistrain PEDV vaccines: Integrating basic concepts and SARS-CoV-2 pan-sarbecovirus strategies(Virology, 2025-01) Fragoso-Saavedra, Mario; Liu, QiangPorcine epidemic diarrhea virus (PEDV) is a major pathogen impacting the global pig industry, with outbreaks causing significant financial losses. The genetic variability of PEDV has posed challenges for vaccine development since its identification in the 1970s, a problem that intensified with its global emergence in the 2010s. Since current vaccines provide limited cross-protection against PEDV strains, and the development of multistrain PEDV vaccines remains an underexplored area of research, there is an urgent need for improved vaccine solutions. The rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and ongoing pan-sarbecovirus vaccine research, have demonstrated the potential of next-generation vaccine platforms and novel antigen design strategies. These advancements offer valuable insights for the development of multistrain PEDV vaccines. This review summarizes key aspects of PEDV virology and explores multistrain vaccine development considering SARS-CoV-2 vaccine innovations, proposing a framework for developing next-generation PEDV vaccine solutions.Item Upregulation of porcine epidemic diarrhea virus (PEDV) RNA translation by the nucleocapsid protein(Virology, 2024-11) Hao, Lin; Fragoso-Saavedra, Mario; Liu, QiangThe role of coronaviral nucleocapsid (N) protein in regulating viral translation remains poorly understood. Here, we showed that the N protein of porcine epidemic diarrhea virus (PEDV) enhances the translation of both virus-like genomic RNA (gRNA) and messenger RNA. Further characterization of the gRNA translation upregulation showed that the N-terminal domain (NTD) + Linker region plays a major role. The stem-loop 1 in the 5′ untranslated region (UTR) and the budged stem loop in the 3′UTR are required for viral translation upregulation by PEDV N protein. The signaling kinase Akt exists in three isoforms. We found that Akt1 enhances viral gRNA translation upregulation by the N protein dependent on its kinase activity. We further showed an interaction between Akt1 and PEDV N, that is abolished by the NTD + Linker region. This suggested that the enhancing effect of Akt1 on translation upregulation by the N protein does not require interaction between these two proteins.Item Grouping Pig-Specific Responses to Mitogen with Similar Responder Animals may Facilitate the Interpretation of Results Obtained in an Out-Bred Animal Model(J Vacc Vaccinol, 2014-04) Wilson, Heather; Pasternak, J. Alex; Ng, Siew Hon; Kaeser, Tobias; Meurens, FrancoisPig peripheral blood-derived mononuclear cells (PBMCs) and lamina propria mononuclear cells (LPMCs) stimulated with mitogens ex vivo can show significant animal-to-animal variation lead to difficulty in interpreting responses in an out-bred animal species. Mixed-cell populations were stimulated ex vivo with 2.5 μg/ml Con A or 2.5 ng/ml PMA plus 250 ng/ml ionomycin (PMAi; (LPCMs only)) or media alone for 72 hours. Supernatants were then tested for cytokine production using a Bioplex assay for porcine IFNα, IFNγ, IL-10, and IL-12. Unstimulated PBMCs had significant levels of IL-10 and the median value for this group decreased in the presence of Con A. Con A did, however, induce production of IFNα and IFNγ, but not IL-12 in this cell population. In contrast, unstimulated and Con A-stimulated LPMCs produced negligible IL-10, IFNα, IFNγ, and the majority of animals’ LPMCs showed negligible IL-12 production in response to Con A. In contrast, LPMCs stimulated with PMAi produced IFNγ suggesting cytokine production is mitogen–specific response. When we tracked animal-specific responses, we observed that discrete subsets of animal’s PBMCs responded to Con A with significantly increased or decreased IL-10 production relative to unstimulated cells. Further, in the LPMCs, some cells produced no IL-12 in response to Con A but showed augmented production in response to PMAi, while others showed production of IL-12 in response to Con A but no response to PMAi. Flow cytometric analysis showed that the PBMCs were a mixture of CD3+ T cells>CD21+ B cells>CD172+ myeloid cells whereas the LPMCs consisted of mainly Cytotoxic T cells and Natural Killer cells. The percentage of CD8α+CD4+ antigen-experienced T cells was greater in the LPMCs relative to the PBMCs. As expected in an out-bred species, animal-specific differences in cytokine production in response to stimulants exist and may confound interpretation of results unless tracked individually.