Canadian Center for Vaccinology

Halifax, Canada

Canadian Center for Vaccinology

Halifax, Canada
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Phadke V.K.,Emory University | Steinhoff M.C.,Cincinnati Childrens Hospital Medical Center | Steinhoff M.C.,Cincinnati Childrens Hospital Global Health Center | Omer S.B.,Emory University | And 2 more authors.
American Journal of Epidemiology | Year: 2016

Maternal influenza immunization can reduce influenza-attributable morbidity and mortality among pregnant women and infants who are too young to be vaccinated. Data from empirical studies also support the hypothesis that immunization can protect the fetus against adverse outcomes if the mother is exposed to influenza. In their theoretical analysis in the Journal, Hutcheon et al. (Am J Epidemiol. 2016;184(3):227-232) critiqued the existing evidence of the fetal benefits of maternal influenza immunization by calculating the sample sizes needed to demonstrate hypothetical reductions in risk and concluded that the benefits observed in empirical studies are likely implausible. However, in their analysis, they did not take into account multiple fundamental characteristics of influenza epidemiology, including the time-variable effects of influenza illness and vaccination during pregnancy, or well-known differences in disease epidemiology between seasons, populations, and geographic regions. Although these and other factors might affect the magnitude of fetal benefit conferred by maternal influenza immunization, studies in which investigators have accounted for influenza circulation have demonstrated a consistent protective effect against a variety of adverse birth outcomes; those studies include the only randomized controlled trial designed a priori and adequately powered to do so. Only a comprehensive and nuanced assessment of the evidence base will allow for effective translation of these data into a global immunization policy. © The Author 2016.

Dube E.,Institute National Of Sante Publique Du Quebec | Dube E.,Laval University | Vivion M.,Institute National Of Sante Publique Du Quebec | Vivion M.,Laval University | And 2 more authors.
Expert Review of Vaccines | Year: 2014

Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of parents. Anti-vaccination movements have been implicated in lowered vaccine acceptance rates and in the increase in vaccine-preventable disease outbreaks and epidemics. In this review, we will look at determinants of parental decision-making about vaccination and provide an overview of the history of anti-vaccination movements and its clinical impact. © 2015 Informa UK Ltd.

Delpeut S.,Dalhousie University | Delpeut S.,Canadian Center for Vaccinology | Sisson G.,Dalhousie University | Black K.M.,Dalhousie University | And 2 more authors.
Journal of Virology | Year: 2017

Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease but has emerged as a promising oncolytic platform. Previous studies of MeV entry focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express the MeV receptors SLAM (signaling lymphocyteactivating molecule) and PVRL4 (poliovirus receptor-like 4) (nectin-4). Recombinant MeVs expressing either firefly luciferase or green fluorescent protein together with a variety of inhibitors were used. The results showed that MeV uptake was dynamin independent in the Vero.hPVRL4, Vero.hSLAM, and PVRL4-positive MCF7 breast cancer cell lines. However, MeV infection was blocked by 5-(N-ethyl-N-propyl)amiloride (EIPA), the hallmark inhibitor of macropinocytosis, as well as inhibitors of actin polymerization. By using phalloidin staining, MeV entry was shown to induce actin rearrangements and the formation of membrane ruffles accompanied by transient elevated fluid uptake. Small interfering RNA (siRNA) knockdown of p21-activated kinase 1 (PAK1) demonstrated that MeV enters both Vero.hPVRL4 and Vero.hSLAM cells in a PAK1-independent manner using a macropinocytosis-like pathway. In contrast, MeV entry into MCF7 human breast cancer cells relied upon Rac1 and its effector PAK1 through a PVRL4-mediated macropinocytosis pathway. MeV entry into DLD-1 colon and HTB-20 breast cancer cells also appeared to use the same pathway. Overall, these findings provide new insight into the life cycle of MeV, which could lead to therapies that block virus entry or methods that improve the uptake of MeV by cancer cells during oncolytic therapy. © 2017 American Society for Microbiology.

Hsu W.-C.,Kaohsiung Medical University | Chang S.-P.,Kaohsiung Medical University | Lin L.-C.,National Health Research Institute | Li C.-L.,Taipei Medical University | And 3 more authors.
Antiviral Research | Year: 2015

A preventive vaccine against hepatitis C virus (HCV) infection remains unavailable and newly developed drugs against viral replication are complicated by potential drug-resistance and high cost. These issues justify the need to develop alternative antiviral agents and expand the scope of strategies for the treatment of hepatitis C, such as targeting viral entry. In this study, we explore the bioactivity of Limonium sinense (L. sinense) and its purified constituents against HCV life cycle using subgenomic replicon and infectious HCV culture systems. Data indicated that the water extract from the underground part of L. sinense (LS-UW) exhibited potent inhibitory activity against HCV at non-cytotoxic concentrations. LS-UW targeted early HCV infection without affecting viral replication, translation, and cell-to-cell transmission, and blocked viral attachment and post-attachment entry/fusion steps. Bioactivity analysis of major constituents from LS-UW through viral infectivity/entry assays revealed that gallic acid (GA) also inhibits HCV entry. Furthermore, both LS-UW and GA could suppress HCV infection of primary human hepatocytes. Due to their potency and ability to target HCV early viral entry, LS-UW and GA may be of value for further development as prospective antivirals against HCV. © 2015 Elsevier B.V. All rights reserved.

Lin L.-T.,Taipei Medical University | Chung C.-Y.,Kaohsiung Medical University | Hsu W.-C.,Kaohsiung Medical University | Chang S.-P.,Kaohsiung Medical University | And 10 more authors.
Journal of Hepatology | Year: 2015

Background & Aims A vaccine against hepatitis C virus (HCV) is unavailable and cost-effective antivirals that prevent HCV infection and re-infection, such as in the transplant setting, do not exist. In a search for novel and economical prophylactic agents, we examined the antiviral activity of saikosaponins (SSa, SSb2, SSc, and SSd) from Bupleurum kaoi root (BK) as entry inhibitors against HCV infection. Methods Infectious HCV culture systems were used to examine the effect of saikosaponins on the complete virus life cycle (entry, RNA replication/translation, and particle production). Antiviral activity against various HCV genotypes, clinical isolates, and infection of primary human hepatocytes were also evaluated. Results BK and the saikosaponins potently inhibited HCV infection at non-cytotoxic concentrations. These natural agents targeted early steps of the viral life cycle, while leaving replication/translation, egress, and spread relatively unaffected. In particular, we identified SSb2 as an efficient inhibitor of early HCV entry, including neutralization of virus particles, preventing viral attachment, and inhibiting viral entry/fusion. Binding analysis, using soluble viral glycoproteins, demonstrated that SSb2 acted on HCV E2. Moreover, SSb2 inhibited infection by several genotypic strains and prevented binding of serum-derived HCV onto hepatoma cells. Finally, treatment with the compound blocked HCV infection of primary human hepatocytes. Conclusions Due to its potency, SSb2 may be of value for development as an antagonist of HCV entry and could be explored as prophylactic treatment during the course of liver transplantation. © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Legge A.,Dalhousie University | Dodds L.,Dalhousie University | Dodds L.,Canadian Center for Vaccinology | MacDonald N.E.,Canadian Center for Vaccinology | And 3 more authors.
CMAJ | Year: 2014

Background: There is growing evidence that seasonal influenza vaccination in pregnancy has benefits for mother and baby. We de - termined influenza vaccination rates among pregnant women during the 2 nonpandemic influenza seasons following the 2009 H1N1 pandemic, explored maternal factors as predictors of influenza vaccination status and evaluated the association between maternal influenza vaccination and neonatal outcomes. Methods:We used a population-based peri natal database in the province of Nova Scotia, Canada, to examine maternal vaccination rates, determinants of vaccination status and neonatal outcomes. Our cohort included wo men who gave birth between Nov. 1, 2010, and Mar. 31, 2012. We compared neonatal outcomes be - tween vaccinated and unvaccinated women using logistic regression analysis. Results: Overall, 1958 (16.0%) of 12 223 wo men in our cohort received the influenza vaccine during their pregnancy. Marital status, parity, location of residence (rural v. urban), smoking during pregnancy and maternal influenza risk status were determinants of maternal vaccine receipt. The odds of preterm birth was lower among infants of vaccinated women than among those of nonvaccinated women (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60-0.94). The rate of lowbirth- weight infants was also lower among vaccinated women (adjusted OR 0.73, 95% CI 0.56-0.95). Interpretation: Despite current guidelines advising all pregnant women to receive the seasonal influenza vaccine, influenza vaccination rates among pregnant women in our cohort were low in the aftermath of the 2009 H1N1 pandemic. This study and others have shown an association between maternal influenza vaccination and improved neonatal outcomes, which supports stronger initiatives to promote vaccination during pregnancy. © 2014 Canadian Medical Association or its licensors.

Cassidy C.,Dalhousie University | Macdonald N.E.,Dalhousie University | Macdonald N.E.,Canadian Center for Vaccinology | Steenbeek A.,Dalhousie University | And 3 more authors.
Pharmacoepidemiology and Drug Safety | Year: 2015

Background: The World Health Organization's Strategic Advisory Group of Experts on Immunization has declared that maternal immunization is a key priority. Robust adverse event following immunization (AEFI) surveillance systems that capture outcomes in pregnant women and their infants are needed to ensure the safety of maternal immunization programs. We sought to identify the active and passive AEFI surveillance systems for pregnant women and their offspring described in the literature. Methods: A systematic literature review was conducted of the MEDLINE, CINAHL, and EMBASE databases from 1990 to 2014. English-language articles were reviewed if they included pregnant women as the population of interest and described the surveillance method used. Results: Of 619 articles retrieved from the search, 16 met the criteria for review. These included reports of AEFI surveillance for pregnant women, their offspring, or both. The majority of reports (11/16) came from the USA and described findings on two active and four passive AEFI surveillance systems, only three of which specifically targeted pregnant women. The remaining five articles described one-time AEFI surveillance programs, all in high-income countries. Conclusion: There are no published reports outside of the USA of ongoing AEFI surveillance systems that specifically target pregnant women or their offspring. There may be AEFI surveillance systems that capture events in these populations that have not been reported in the literature. A survey of immunization program managers and national regulatory authorities is needed to determine the current status of AEFI surveillance for pregnant women and their offspring globally. © 2015 John Wiley & Sons, Ltd.

Brown M.G.,Dalhousie University | Brown M.G.,Canadian Center for Vaccinology | McAlpine S.M.,Dalhousie University | Huang Y.Y.,Dalhousie University | And 7 more authors.
PLoS ONE | Year: 2012

Dengue hemorrhagic fever and/or dengue shock syndrome represent the most serious pathophysiological manifestations of human dengue virus infection. Despite intensive research, the mechanisms and important cellular players that contribute to dengue disease are unclear. Mast cells are tissue-resident innate immune cells that play a sentinel cell role in host protection against infectious agents via pathogen-recognition receptors by producing potent mediators that modulate inflammation, cell recruitment and normal vascular homeostasis. Most importantly, mast cells are susceptible to antibody-enhanced dengue virus infection and respond with selective cytokine and chemokine responses. In order to obtain a global view of dengue virus-induced gene regulation in mast cells, primary human cord blood-derived mast cells (CBMCs) and the KU812 and HMC-1 mast cell lines were infected with dengue virus in the presence of dengue-immune sera and their responses were evaluated at the mRNA and protein levels. Mast cells responded to antibody-enhanced dengue virus infection or polyinosiniċpolycytidylic acid treatment with the production of type I interferons and the rapid and potent production of chemokines including CCL4, CCL5 and CXCL10. Multiple interferon-stimulated genes were also upregulated as well as mRNA and protein for the RNA sensors PKR, RIG-I and MDA5. Dengue virus-induced chemokine production by KU812 cells was significantly modulated by siRNA knockdown of RIG-I and PKR, in a negative and positive manner, respectively. Pretreatment of fresh KU812 cells with supernatants from dengue virus-infected mast cells provided protection from subsequent infection with dengue virus in a type I interferon-dependent manner. These findings support a role for tissue-resident mast cells in the early detection of antibody-enhanced dengue virus infection via RNA sensors, the protection of neighbouring cells through interferon production and the potential recruitment of leukocytes via chemokine production. © 2012 Brown et al.

Al-Afif A.,Dalhousie University | Alyazidi R.,Dalhousie University | Alyazidi R.,King Abdulaziz University | Oldford S.A.,Dalhousie University | And 6 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Respiratory syncytial virus (RSV) causes severe respiratory tract infections, which might have a role in the development of airway hyperreactivity. Mast cells are important effector cells in allergy, with sentinel cell roles in host defense. However, the role of mast cells in response to RSV infection is unknown. Objective Human mast cell responses to RSV were investigated with a view to better understanding the role of mast cells in RSV-induced disease. Methods Human cord blood-derived mast cells and the HMC-1 mast cell line were exposed to RSV or UV-inactivated RSV. Viral gene and protein expression were evaluated by using PCR and flow cytometry. The expression of interferon-stimulated genes and selected mediators were evaluated by using quantitative PCR and ELISA. Results Human mast cells expressed multiple RSV genes after exposure to RSV, and a small percentage of mast cells supported RSV antigen protein expression. RSV induced mast cells to upregulate production of chemokines, including CCL4, CCL5, and CXCL10, as well as type I interferons, and interferon-stimulated gene expression. However, production of the granulocyte chemoattractants CXCL8 and CCL11 was not induced. Antibody blockade of the type I interferon receptor on human cord blood-derived mast cells reduced the RSV-mediated induction of CXCL10 and CCL4 but not CCL5. Leukotriene C4 production by mast cells was not enhanced by exposure to RSV. Conclusion Despite low levels of infection, human mast cells produce multiple chemokines in response to RSV through mechanisms that include responses to type I interferons. Such mast cell responses might enhance effector cell recruitment during RSV-induced disease. © 2015 The Authors. Published by Elsevier Inc.

Wisner A.L.S.,University of Saskatchewan | Wisner A.L.S.,Canadian Center for Vaccinology | Potter A.A.,University of Saskatchewan | Koster W.,University of Saskatchewan
PLoS ONE | Year: 2011

In order to better identify the role of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (T3SS) in chickens, we used the well-known gentamicin protection assay with activated HD11 cells. HD11 cells are a macrophage-like chicken cell line that can be stimulated with phorbol 12-myristate 13-acetate (PMA) to exhibit more macrophage-like morphology and greater production of reactive oxygen species (ROS). Activated HD11 cells were infected with a wild-type Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) strain, a SPI-2 mutant S. Typhimurium strain, a wild-type Salmonella enterica subspecies enterica serovar Enteritidis (S. Enteritidis) strain, a SPI-2 mutant S. Enteritidis strain, or a non-pathogenic Escherichia coli (E. coli) strain. SPI-2 mutant strains were found to survive as well as their parent strain at all time points post-uptake (PU) by the HD11 cells, up to 24 h PU, while the E. coli strain was no longer recoverable by 3 h PU. We can conclude from these observations that the SPI-2 T3SS of S. Typhimurium and S. Enteritidis is not important for survival of Salmonella in the activated macrophage-like HD11 cell line, and that Salmonella must employ other mechanisms for survival in this environment, as E. coli is effectively eliminated. © 2011 Wisner et al.

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