L A Babiuk

University of Alberta, Edmonton, Alberta, Canada

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Publications (644)1999.25 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Protective efficacy against bovine herpesvirus-1 (BoHV-1) has been demonstrated to be induced by a plasmid encoding the bovine beta-defensin, BNBD3, as a fusion with a truncated version of glycoprotein D (tgD). However, in spite of the increased cell-mediated immune responses induced by this DNA vaccine, the clinical responses of BoHV-1 challenged cattle were not reduced over those observed in animals vaccinated with the plasmid encoding tgD alone; this may have been because the vaccine failed to improve the humoral response. We hypothesized that an alternative vaccine design strategy, that utilized DNA vaccine pMASIA-tgD as a complex with BNBD3 peptide, might improve the humoral response while maintaining a robust Th1-type cell-mediated response. C57Bl/6 mice were vaccinated with pMASIA-tgD complexed with 0, 0.01875, 0.1875, or 1.875 nmol of a stable synthesized analog of BNBD3 (aBNBD3). The best results were seen in mice immunized with the vaccine comprised of pMASIA-tgD complexed to 0.1875 nmol aBNBD3. In this group the humoral response was improved as evidenced in increased VN, tgD-specific early IgG1 and later IgG2a; while the strong cell-mediated immune response, measured based on specific IFN-γ-secreting cells, was maintained relative to pMASIA-tgD. Modulation of the immune response may have been due in part to the effect of BNBD3 on dendritic cells (DCs). In vitro studies showed that murine bone marrow-derived DCs (BMDCs) pre-treated with aBNBD3 were activated as evidenced by down-regulated CD11c and were functionally matured as shown by increased allostimulatory ability. Native, synthesized and analog BNBD3 were equally capable of inducing functional maturation of BMDCs.
    Clinical and vaccine Immunology: CVI 11/2014; 22(1). DOI:10.1128/CVI.00476-14 · 2.37 Impact Factor
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    ABSTRACT: Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required.
    PLoS ONE 10/2014; 9(10):e109778. DOI:10.1371/journal.pone.0109778 · 3.53 Impact Factor
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    ABSTRACT: One of the impediments in the development of safe and cost effective vaccines for veterinary use has been the availability of appropriate delivery vehicle. We have chosen to develop and use bovine adenovirus (BAdV)-3 as vaccine delivery vector in cattle. Here, we describe the construction of recombinant E3 deleted BAdV-3 vectors expressing single vaccine antigen (BAV360; bovine respiratory syncytial virus G) or two vaccine antigens (BAV851; bovine herpesvirus-1gDt and bovine respiratory syncytial virus G). Recombinant proteins expressed by BAV360 or BAV851 were recognized by protein-specific monoclonal antibodies. Moreover, intranasal immunization of cotton rats with BAV360 (expressing a single vaccine antigen) or BAV851 (expressing two vaccine antigens) induced strong antigen-specific immune responses. These results suggest that single replication-competent BAdV-3 expressing vaccine antigens of two economically important respiratory pathogens of calves has potential to act as a feasible approach in the development of economically effective veterinary vaccines for cattle.
    Molecular Biotechnology 08/2014; 57(1). DOI:10.1007/s12033-014-9801-x · 2.28 Impact Factor
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    ABSTRACT: The process of virus replication in host cells is greatly influenced by the set of cytokines, chemokines and antiviral substances activated as a result of host-virus interaction. Alteration of cytokines profiles through manipulation of the innate immune system by innate immune stimulants may be helpful in inhibiting virus replication in otherwise permissive cells. The aim of present studies was to characterize innate immune responses capable of inhibiting infectious bronchitis virus (IBV) replication in chicken lungs after in ovo administration of CpG ODN. In our experiments, CpG ODN 2007 or PBS solution was injected on 18th embryonic day (ED) via the chorioallontoic route. CpG ODN and PBS inoculated embryos were challenged with virulent IBV on the 19th ED. Lung tissue samples from experimental chicks were analyzed for cytokines/chemokines gene expression at 24 hrs, 48 hrs, and 72 hrs, post infection. Our data showed significant differential up-regulation of IFN-γ, IL-8 (CXCLi2) and MIP-1β genes and suppression of IL-6 gene expression being associated with inhibition of IBV replication in lungs tissue retrieved from embryos pre-treated with CpG ODN. It is expected that understanding of the innate immune modulation of target tissues by the virus and innate immune stimulants will be helpful in identification of valuable targets for development of novel, safe, effective and economical control strategies against IBV infection in chickens.
    Veterinary Immunology and Immunopathology 08/2014; 160(3-4). DOI:10.1016/j.vetimm.2014.05.004 · 1.75 Impact Factor
  • 06/2014; 2:500-514. DOI:10.3390/vaccines2030500
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    ABSTRACT: Previous studies have suggested an important role of the cytokine adjuvant IL-6 in the induction of mucosal immune responses in animals, including mice. Here, we report the in vivo ability of bovine adenovirus (BAdV)-3 expressing bovine (Bo) IL-6, to influence the systemic and mucosal immune responses against bovine herpesvirus (BHV)-1 gDt in calves. To co-express both antigen and cytokine, we first constructed a recombinant BAdV-3 expressing chimeric gDt.BoIL-6 protein (BAV326). Secondly, we constructed another recombinant BAdV-3 simultaneously expressing gDt and BoIL-6 using IRES containing a bicistronic cassette gDt-IRES.IL-6, (BAV327). Recombinant proteins expressed by BAV326 and BAV327 retained antigenicity (gDt) and biological activity (BoIL-6). Intranasal immunization of calves with recombinant BAV326, BAV327 or BAV308 (gDt alone) resulted in demonstrable levels of gDt-specific IgG responses in sera and IgA response in nasal secretions, in all animals. In addition, all calves developed complement-independent neutralizing antibody responses against BHV-1. However, no significant difference could be observed in the induction of systemic or mucosal immune response in animals immunized with recombinant BAV326 or BAV327 co-expressing BoIL-6. Moreover, there was no difference in the protection against BHV-1 challenge particularly in the amount of virus excretion in the nasal cavity in calves immunized with BAV326, BAV327 or BAV308. These data suggest that the BoIL-6 had no modulating effect on the induction of gDt specific mucosal and systemic immune responses in calves.
    Vaccine 04/2014; 32(26). DOI:10.1016/j.vaccine.2014.03.073 · 3.49 Impact Factor
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    ABSTRACT: We recently reported a novel interleukin-10 (IL-10)-secreting CD21(+) B cell population in jejunal Peyer's patches (JPP) of sheep with a regulatory function (Bregs) suppressing Toll-like receptor 9 (TLR9)-induced cytokine responses. However, little is known about the development of these cells. Therefore, we investigate their existence in JPP cells from fetal and newborn lambs. CD21(+) B cells were purified from JPP cells by magnetic cell sorting and subsequently stimulated with the TLR9 agonist, CpG ODN (CpG oligodeoxynucleotide). Lymphocyte proliferative responses, cytokine production (IL-10, IL-12 and interferon-γ [INF-γ]) and antibody secretion were assayed. We found that fetal and neonatal CD21(+) B cells spontaneously secreted high levels of IL-10 regardless of CpG stimulation but that these cells did not produce any IL-12 or INF-γ upon stimulation with CpG. The observed responses are consistent with those previously reported for Bregs characterized in JPP of older lambs. Surprisingly, unlike in older lambs, fetal and neonatal JPP CD21(+) B cells proliferated in response to CpG stimulation. Our investigations of fetal and neonatal lambs provide evidence for the development of IL-10-secreting CD21(+) B cells in PPs prior to antigen exposure.
    Cell and Tissue Research 04/2014; 356(2). DOI:10.1007/s00441-014-1803-2 · 3.33 Impact Factor
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    ABSTRACT: Poly[di(sodiumcarboxylatoethylphenoxy)phosphazene] (PCEP) has shown great potential as a vaccine adjuvant, but the mechanisms that mediate its adjuvant activity have not been investigated. Previously, we had reported the potential of PCEP to induce cytokines and chemokines at the site of injection. Hence, we hypothesized that PCEP creates strong immuno-competent environment leading to recruitment of immune cells at the injection site. Intramuscular injection of mice with PCEP induced significant recruitment of neutrophils, macrophages, monocytes, dendritic cells (DCs), and lymphocytes at the site of injection as well as in the draining lymph nodes. Flow cytometric analysis showed that the majority of the recruited immune cells took up and/or were associated with PCEP at the injection site, with lymphocytes taking up PCEP in lesser quantity. Further, confocal analysis revealed intracytoplasmic lysosomal localization of PCEP in recruited immune cells. These observations suggest that recruitment of distinct immune cells to the site of injection site may be an important mechanism by which PCEP potentiates immune responses to antigens.
    Vaccine 03/2014; 32(21). DOI:10.1016/j.vaccine.2014.03.014 · 3.49 Impact Factor
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    ABSTRACT: Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions. Citation: Truong T, Boshra H, Embury-Hyatt C, Nfon C, Gerdts V, et al. (2014) Peste des Petits Ruminants Virus Tissue Tropism and Pathogenesis in Sheep and Goats following Experimental Infection. PLoS ONE 9(1): e87145. doi:10.1371/journal.pone.0087145 Copyright: ß 2014 Truong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded from a Canadian International Food Security Research Fund (CIFSRF) grant (no. 106930: Livestock vaccines against viral diseases for sub-Saharan Africa) by the Canadian International Development Research Centre (IDRC) and Canadian International Development Agency (CIDA) and is supported by the respective research institutions to which the authors belong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
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    ABSTRACT: Bovine herpesvirus-1 (BoHV-1) causes recurrent respiratory and genital infections in cattle, and predisposes them to lethal secondary infections. While modified-live and killed BoHV-1 vaccines exist, these are not without problems. Development of an effective DNA vaccine for BoHV-1 has the potential to address these issues. As a strategy to enhance DNA vaccine immunity, a plasmid encoding the bovine neutrophil beta defensin-3 (BNBD3) as a fusion with truncated glycoprotein D (tgD) and a mix of two plasmids encoding BNBD3 and tgD were tested in mice and cattle. In mice, co-administration of BNBD3 on the separate plasmid enhanced the tgD-induced IFN-γ response, but not the antibody response. BNBD3 fused to tgD did not affect the antibody levels or the number of IFN-γ secreting cells, but increased the induction of tgD-specific cytotoxic T lymphocytes (CTLs). In cattle, the addition of BNBD3 as a fusion construct modified the immune response. In cattle, the addition of BNBD3 as a fusion construct also modified the immune response. While the IgG and virus neutralizing antibody levels were not affected, the number of IFN-γ secreting cells was increased; specifically the CD8(+)/IFN-γ(+) T cells including CD8(+)/IFN-γ(+)/CD25(+) CTLs after BoHV-1 challenge. While reduced virus shedding, rectal temperature and weight loss were observed, the level of protection was comparable to that observed in pMASIA-tgD-vaccinated animals. These data show that co-administration of BNBD3 with a protective antigen as a fusion in a DNA vaccine strengthened the Th1 bias and increased cell-mediated immune responses, but did not enhance protection from BoHV-1 infection.
    Clinical and vaccine Immunology: CVI 01/2014; DOI:10.1128/CVI.00696-13 · 2.37 Impact Factor
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    ABSTRACT: Peste des petits ruminants (PPR) is a viral disease which primarily affects small ruminants, causing significant economic losses for the livestock industry in developing countries. It is endemic in Saharan and sub-Saharan Africa, the Middle East and the Indian sub-continent. The primary hosts for peste des petits ruminants virus (PPRV) are goats and sheep; however recent models studying the pathology, disease progression and viremia of PPRV have focused primarily on goat models. This study evaluates the tissue tropism and pathogenesis of PPR following experimental infection of sheep and goats using a quantitative time-course study. Upon infection with a virulent strain of PPRV, both sheep and goats developed clinical signs and lesions typical of PPR, although sheep displayed milder clinical disease compared to goats. Tissue tropism of PPRV was evaluated by real-time RT-PCR and immunohistochemistry. Lymph nodes, lymphoid tissue and digestive tract organs were the predominant sites of virus replication. The results presented in this study provide models for the comparative evaluation of PPRV pathogenesis and tissue tropism in both sheep and goats. These models are suitable for the establishment of experimental parameters necessary for the evaluation of vaccines, as well as further studies into PPRV-host interactions.
    PLoS ONE 01/2014; 9(1):e87145. DOI:10.1371/journal.pone.0087145 · 3.53 Impact Factor
  • Lorne A Babiuk
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    ABSTRACT: Infectious diseases continue to cause significant morbidity and mortality in both animals and humans. Indeed, every year infectious diseases cost the global economy billions of dollars in losses and are responsible for approximately one-third of all human deaths. These deaths occur from routine infections, hospital acquired infections (approximately 100,000 deaths occur annually in North America due to hospital-acquired infections), occasional pandemics or regional outbreaks. The most recent regional outbreak is Ebola in West Africa. This infection has caused significant challenges for the regional health care community and has had a global impact. The challenge in the control of infectious diseases is not only due to routine infections but also to the continued emergence and re-emergence of infectious diseases. These new threats occur on a regular basis with approximately thirty new emerging or re-emerging diseases recorded in the last thirty years. The majority of these emerging diseases are zoonotic (over 70%) causing even greater challenges to their control in humans and animals.
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    Sunita Awate, Lorne A Babiuk, George Mutwiri
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    ABSTRACT: Adjuvants are used in many vaccines, but their mechanisms of action are not fully understood. Studies from the past decade on adjuvant mechanisms are slowly revealing the secrets of adjuvant activity. In this review, we have summarized the recent progress in our understanding of the mechanisms of action of adjuvants. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. It appears that adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses. Understanding the mechanisms of action of adjuvants will provide critical information on how innate immunity influences the development of adaptive immunity, help in rational design of vaccines against various diseases, and can inform on adjuvant safety.
    Frontiers in Immunology 05/2013; 4:114. DOI:10.3389/fimmu.2013.00114
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    ABSTRACT: Whooping cough is a respiratory illness most severe in infants and young children. While the introduction of whole-cell (wP) and acellular pertussis (aP) vaccines has greatly reduced the burden of the disease, pertussis remains a problem in neonates and adolescents. New vaccines are needed that can provide early life and long-lasting protection of infants. Vaccination at an early age, however, is problematic due to the interference with maternally derived antibodies (MatAbs) and the bias towards Th2-type responses following vaccination. Here we report the development of a novel vaccine formulation against pertussis that is highly protective in the presence of MatAbs. We co-formulated pertussis toxoid (PTd) and filamentous hemagglutinin (FHA) with cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN), cationic innate defense regulator (IDR) peptide and polyphosphazene (PP) into microparticle and soluble vaccine formulations and tested them in murine and porcine models in the presence and absence of passive immunity. Vaccines composed of the new adjuvant formulations induced an earlier onset of immunity, higher anti-pertussis IgG2a and IgA titers, and a balanced Th1/Th2-type responses when compared to immunization with Quadracel(®), one of the commercially available vaccines for pertussis. Most importantly, the vaccines offered protection against challenge infection in the presence of passively transferred MatAbs.
    Vaccine 05/2013; 31(31). DOI:10.1016/j.vaccine.2013.05.008 · 3.49 Impact Factor
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    ABSTRACT: The neonatal immune system is often considered as immature or impaired compared to the adult immune system. This higher susceptibility to infections is partly due to the skewing of the neonatal immune response towards a Th2 response. Activation and maturation of dendritic cells (DCs) play an important role in shaping the immune response, therefore, DCs are a target of choice for the development of efficient and protective vaccine formulations able to redirect the neonatal immune response to a protective Th1 response. As pigs are becoming more important for vaccine development studies due to their similarity to the human immune system, we decided to compare the activation and maturation of a subpopulation of porcine DCs in adult and neonatal pigs following stimulation with different TLR ligands, which are promising candidates for adjuvants in vaccine formulations. Porcine blood derived DCs (BDCs) were directly isolated from blood and consisted of a mix of conventional and plasmacytoid DCs. Following CpG ODN (TLR9 ligand) and imiquimod (TLR7 ligand) stimulation, neonatal BDCs showed higher levels of expression of costimulatory molecules and similar (CpG ODN) or higher (imiquimod) levels of IL-12 compared to adult BDCs. Another interesting feature was that only neonatal BDCs produced IFN-α after TLR7 or TLR9 ligand stimulation. Stimulation with CpG ODN and imiquimod also induced enhanced expression of several chemokines. Moreover, in a mixed leukocyte reaction assay, neonatal BDCs displayed a greater ability to induce lymphoproliferation. These findings suggest that when stimulated via TLR7 or TLR9 porcine DCs display similar if not better response than adult porcine DCs.
    PLoS ONE 05/2013; 8(5):e59629. DOI:10.1371/journal.pone.0059629 · 3.53 Impact Factor
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    ABSTRACT: Five different viral diseases of livestock, lumpy skin disease (LSD), sheep pox (SPP), goat pox (GTP), Rift Valley fever (RVF) and peste des petits ruminants (PPR), circulate in the same regions of Africa, imposing a major burden on economic activity and public health. While commercial vaccines against these viruses are available, the cost of implementing regular vaccination regimens against multiple diseases is prohibitive for most African farmers. A single, affordable multivalent vaccine that simultaneously protects against all 5 diseases would therefore be of significant benefit to the livestock sector in Africa. It could also serve as a platform for the development of new vaccines of significance to other developing countries around the world. In this paper, we present an overview of the economic importance of livestock in Africa, the pathogens responsible for RVF, PPR, SPP, GTP and LSD and the vaccination strategies currently used to combat them. We then review experience with the development of attenuated capripoxviruses as vaccines against LSD, SPP and GTP and of recombinant capripoxvirus-vectored vaccines against RVF and PPR. We conclude the article by presenting the rationale for a single, multivalent capripoxvirus-vectored vaccine that would protect against all 5 diseases of livestock, and describe the approach being taken by a consortium of Canadian and South African researchers to develop such a vaccine.
    Antiviral research 03/2013; DOI:10.1016/j.antiviral.2013.02.016 · 3.94 Impact Factor
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    ABSTRACT: a b s t r a c t Five different viral diseases of livestock, lumpy skin disease (LSD), sheep pox (SPP), goat pox (GTP), Rift Valley fever (RVF) and peste des petits ruminants (PPR), circulate in the same regions of Africa, imposing a major burden on economic activity and public health. While commercial vaccines against these viruses are available, the cost of implementing regular vaccination regimens against multiple diseases is prohib-itive for most African farmers. A single, affordable multivalent vaccine that simultaneously protects against all 5 diseases would therefore be of significant benefit to the livestock sector in Africa. It could also serve as a platform for the development of new vaccines of significance to other developing countries around the world. In this paper, we present an overview of the economic importance of livestock in Africa, the pathogens responsible for RVF, PPR, SPP, GTP and LSD and the vaccination strategies currently used to combat them. We then review experience with the development of attenuated capripoxviruses as vaccines against LSD, SPP and GTP and of recombinant capripoxvirus-vectored vaccines against RVF and PPR. We conclude the article by presenting the rationale for a single, multivalent capripoxvirus-vectored vaccine that would protect against all 5 diseases of livestock, and describe the approach being taken by a consortium of Canadian and South African researchers to develop such a vaccine. Crown Copyright Ó 2013 Published by Elsevier B.V. All rights reserved.
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    ABSTRACT: Please cite this paper as: Kim et al. (2012) Characteristics of respiratory viral infections during influenza season in Canadian Hutterite Communities. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12021. Objectives:  To determined the pathogen-specific incidence of respiratory virus infection in Hutterite communities occurring over the 2008-2009 influenza season and assess temporal characteristics of respiratory illness related to infection. Methods:  3273 participants community members enrolled in a cluster randomized trial of influenza vaccine were studied. Results:  One hundred forty-nine participants had laboratory-confirmed influenza, and 595 had at least one episode of laboratory-confirmed respiratory viral infection other than influenza. Entero/rhinovirus had the highest incidence among children <5 years. Conclusions:  A decline in the incidence of infections with age was observed for influenza as well as for most other respiratory viruses.
    Influenza and Other Respiratory Viruses 10/2012; 7(6). DOI:10.1111/irv.12021 · 1.90 Impact Factor

Publication Stats

15k Citations
1,999.25 Total Impact Points

Institutions

  • 2008–2014
    • University of Alberta
      Edmonton, Alberta, Canada
    • National Veterinary Research Quarantine Service
      Sŏul, Seoul, South Korea
  • 1974–2014
    • University of Saskatchewan
      • • Vaccine and Infectious Disease Organization
      • • Department of Veterinary Microbiology
      • • Western College of Veterinary Medicine
      Saskatoon, Saskatchewan, Canada
  • 2011
    • University of Ottawa
      • Department of Biochemistry, Microbiology and Immunology
      Ottawa, Ontario, Canada
  • 2006
    • Canadian Food Inspection Agency
      Fredericton, New Brunswick, Canada
  • 1997
    • University of Guelph
      Guelph, Ontario, Canada
  • 1994
    • United Arab Emirates University
      • Department of Biochemistry
      Al Ain, Abu Dhabi, United Arab Emirates