Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
Identifieur interne : 000281 ( Main/Exploration ); précédent : 000280; suivant : 000282Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
Auteurs : Danuta M. Skowronski [Canada] ; Naveed Z. Janjua [Canada] ; Gaston De Serres [Canada] ; Suzana Sabaiduc [Canada] ; Alireza Eshaghi [Canada] ; James A. Dickinson [Canada] ; Kevin Fonseca [Canada] ; Anne-Luise Winter [Canada] ; Jonathan B. Gubbay [Canada] ; Mel Krajden [Canada] ; Martin Petric [Canada] ; Hugues Charest [Canada] ; Nathalie Bastien [Canada] ; Trijntje L. Kwindt [Canada] ; Salaheddin M. Mahmud [Canada] ; Paul Van Caeseele [Canada] ; Yan Li [Canada]Source :
- PloS one [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- ADN viral (génétique), Adolescent (MeSH), Adulte (MeSH), Adulte d'âge moyen (MeSH), Canada (MeSH), Conformation des protéines (MeSH), Données de séquences moléculaires (MeSH), Enfant (MeSH), Enfant d'âge préscolaire (MeSH), Femelle (MeSH), Glycoprotéine hémagglutinine du virus influenza (génétique), Glycoprotéine hémagglutinine du virus influenza (immunologie), Grippe humaine (génétique), Grippe humaine (immunologie), Grippe humaine (prévention et contrôle), Grippe humaine (virologie), Humains (MeSH), Immunisation (MeSH), Jeune adulte (MeSH), Mutation (génétique), Mâle (MeSH), Nourrisson (MeSH), Nouveau-né (MeSH), Saisons (MeSH), Sous-type H3N2 du virus de la grippe A (génétique), Sous-type H3N2 du virus de la grippe A (immunologie), Sous-type H3N2 du virus de la grippe A (isolement et purification), Sujet âgé (MeSH), Sujet âgé de 80 ans ou plus (MeSH), Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (immunologie), Études cas-témoins (MeSH).
- MESH :
- administration et posologie : Vaccins antigrippaux.
- génétique : ADN viral, Glycoprotéine hémagglutinine du virus influenza, Grippe humaine, Mutation, Sous-type H3N2 du virus de la grippe A.
- immunologie : Glycoprotéine hémagglutinine du virus influenza, Grippe humaine, Sous-type H3N2 du virus de la grippe A, Vaccins antigrippaux.
- isolement et purification : Sous-type H3N2 du virus de la grippe A.
- prévention et contrôle : Grippe humaine.
- virologie : Grippe humaine.
- Adolescent, Adulte, Adulte d'âge moyen, Canada, Conformation des protéines, Données de séquences moléculaires, Enfant, Enfant d'âge préscolaire, Femelle, Humains, Immunisation, Jeune adulte, Mâle, Nourrisson, Nouveau-né, Saisons, Sujet âgé, Sujet âgé de 80 ans ou plus, Études cas-témoins.
- Wicri :
- geographic : Canada.
English descriptors
- KwdEn :
- Adolescent (MeSH), Adult (MeSH), Aged (MeSH), Aged, 80 and over (MeSH), Canada (MeSH), Case-Control Studies (MeSH), Child (MeSH), Child, Preschool (MeSH), DNA, Viral (genetics), Female (MeSH), Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Humans (MeSH), Immunization (MeSH), Infant (MeSH), Infant, Newborn (MeSH), Influenza A Virus, H3N2 Subtype (genetics), Influenza A Virus, H3N2 Subtype (immunology), Influenza A Virus, H3N2 Subtype (isolation & purification), Influenza Vaccines (administration & dosage), Influenza Vaccines (immunology), Influenza, Human (genetics), Influenza, Human (immunology), Influenza, Human (prevention & control), Influenza, Human (virology), Male (MeSH), Middle Aged (MeSH), Molecular Sequence Data (MeSH), Mutation (genetics), Protein Conformation (MeSH), Seasons (MeSH), Young Adult (MeSH).
- MESH :
- chemical , administration & dosage : Influenza Vaccines.
- chemical , genetics : DNA, Viral, Hemagglutinin Glycoproteins, Influenza Virus.
- chemical , immunology : Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines.
- geographic : Canada.
- genetics : Influenza A Virus, H3N2 Subtype, Influenza, Human, Mutation.
- immunology : Influenza A Virus, H3N2 Subtype, Influenza, Human.
- isolation & purification : Influenza A Virus, H3N2 Subtype.
- prevention & control : Influenza, Human.
- virology : Influenza, Human.
- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Child, Preschool, Female, Humans, Immunization, Infant, Infant, Newborn, Male, Middle Aged, Molecular Sequence Data, Protein Conformation, Seasons, Young Adult.
Abstract
BACKGROUND
Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.
METHODS/FINDINGS
Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses.
CONCLUSIONS
These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.
DOI: 10.1371/journal.pone.0092153
PubMed: 24667168
PubMed Central: PMC3965421
Affiliations:
- Canada
- Alberta, Manitoba, Ontario, Québec
- Calgary, Québec (ville), Toronto, Winnipeg
- Université Laval, Université de Calgary, Université de Toronto, Université du Manitoba
Links toward previous steps (curation, corpus...)
Le document en format XML
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Dickinson</name><affiliation wicri:level="4"><nlm:affiliation>Family Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Family Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta</wicri:regionArea><orgName type="university">Université de Calgary</orgName><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Fonseca, Kevin" sort="Fonseca, Kevin" uniqKey="Fonseca K" first="Kevin" last="Fonseca">Kevin Fonseca</name><affiliation wicri:level="4"><nlm:affiliation>Department of Virology, Provincial Laboratory of Public Health, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Virology, Provincial Laboratory of Public Health, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta</wicri:regionArea><orgName type="university">Université de Calgary</orgName><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Winter, Anne Luise" sort="Winter, Anne Luise" uniqKey="Winter A" first="Anne-Luise" last="Winter">Anne-Luise Winter</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control, Public Health Ontario, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control, Public Health Ontario, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Gubbay, Jonathan B" sort="Gubbay, Jonathan B" uniqKey="Gubbay J" first="Jonathan B" last="Gubbay">Jonathan B. Gubbay</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology, Public Health Ontario, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Microbiology, Public Health Ontario, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Krajden, Mel" sort="Krajden, Mel" uniqKey="Krajden M" first="Mel" last="Krajden">Mel Krajden</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Petric, Martin" sort="Petric, Martin" uniqKey="Petric M" first="Martin" last="Petric">Martin Petric</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Charest, Hugues" sort="Charest, Hugues" uniqKey="Charest H" first="Hugues" last="Charest">Hugues Charest</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada; Département De Microbiologie, Infectiologie et Immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada; Département De Microbiologie, Infectiologie et Immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Bastien, Nathalie" sort="Bastien, Nathalie" uniqKey="Bastien N" first="Nathalie" last="Bastien">Nathalie Bastien</name><affiliation wicri:level="1"><nlm:affiliation>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Kwindt, Trijntje L" sort="Kwindt, Trijntje L" uniqKey="Kwindt T" first="Trijntje L" last="Kwindt">Trijntje L. Kwindt</name><affiliation wicri:level="1"><nlm:affiliation>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Mahmud, Salaheddin M" sort="Mahmud, Salaheddin M" uniqKey="Mahmud S" first="Salaheddin M" last="Mahmud">Salaheddin M. Mahmud</name><affiliation wicri:level="4"><nlm:affiliation>Community Health Sciences and Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Community Health Sciences and Pharmacy, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Van Caeseele, Paul" sort="Van Caeseele, Paul" uniqKey="Van Caeseele P" first="Paul" last="Van Caeseele">Paul Van Caeseele</name><affiliation wicri:level="4"><nlm:affiliation>Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><affiliation wicri:level="4"><nlm:affiliation>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24667168</idno><idno type="pmid">24667168</idno><idno type="doi">10.1371/journal.pone.0092153</idno><idno type="pmc">PMC3965421</idno><idno type="wicri:Area/Main/Corpus">000285</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000285</idno><idno type="wicri:Area/Main/Curation">000285</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000285</idno><idno type="wicri:Area/Main/Exploration">000285</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.</title><author><name sortKey="Skowronski, Danuta M" sort="Skowronski, Danuta M" uniqKey="Skowronski D" first="Danuta M" last="Skowronski">Danuta M. Skowronski</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Janjua, Naveed Z" sort="Janjua, Naveed Z" uniqKey="Janjua N" first="Naveed Z" last="Janjua">Naveed Z. Janjua</name><affiliation wicri:level="1"><nlm:affiliation>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="De Serres, Gaston" sort="De Serres, Gaston" uniqKey="De Serres G" first="Gaston" last="De Serres">Gaston De Serres</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biological and Occupational Risks, Institut National de Santé Publique du Québec, Québec (Québec), Canada; Department of Social and Preventive Medicine, Laval University, Québec (Québec), Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biological and Occupational Risks, Institut National de Santé Publique du Québec, Québec (Québec), Canada; Department of Social and Preventive Medicine, Laval University, Québec (Québec)</wicri:regionArea><orgName type="university">Université Laval</orgName><placeName><settlement type="city">Québec (ville)</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Sabaiduc, Suzana" sort="Sabaiduc, Suzana" uniqKey="Sabaiduc S" first="Suzana" last="Sabaiduc">Suzana Sabaiduc</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Eshaghi, Alireza" sort="Eshaghi, Alireza" uniqKey="Eshaghi A" first="Alireza" last="Eshaghi">Alireza Eshaghi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Molecular Research, Public Health Ontario, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Molecular Research, Public Health Ontario, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Dickinson, James A" sort="Dickinson, James A" uniqKey="Dickinson J" first="James A" last="Dickinson">James A. Dickinson</name><affiliation wicri:level="4"><nlm:affiliation>Family Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Family Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta</wicri:regionArea><orgName type="university">Université de Calgary</orgName><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Fonseca, Kevin" sort="Fonseca, Kevin" uniqKey="Fonseca K" first="Kevin" last="Fonseca">Kevin Fonseca</name><affiliation wicri:level="4"><nlm:affiliation>Department of Virology, Provincial Laboratory of Public Health, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Virology, Provincial Laboratory of Public Health, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta</wicri:regionArea><orgName type="university">Université de Calgary</orgName><placeName><settlement type="city">Calgary</settlement><region type="state">Alberta</region></placeName></affiliation></author><author><name sortKey="Winter, Anne Luise" sort="Winter, Anne Luise" uniqKey="Winter A" first="Anne-Luise" last="Winter">Anne-Luise Winter</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control, Public Health Ontario, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control, Public Health Ontario, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Gubbay, Jonathan B" sort="Gubbay, Jonathan B" uniqKey="Gubbay J" first="Jonathan B" last="Gubbay">Jonathan B. Gubbay</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology, Public Health Ontario, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Microbiology, Public Health Ontario, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Krajden, Mel" sort="Krajden, Mel" uniqKey="Krajden M" first="Mel" last="Krajden">Mel Krajden</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Petric, Martin" sort="Petric, Martin" uniqKey="Petric M" first="Martin" last="Petric">Martin Petric</name><affiliation wicri:level="1"><nlm:affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Charest, Hugues" sort="Charest, Hugues" uniqKey="Charest H" first="Hugues" last="Charest">Hugues Charest</name><affiliation wicri:level="1"><nlm:affiliation>Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada; Département De Microbiologie, Infectiologie et Immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada; Département De Microbiologie, Infectiologie et Immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Bastien, Nathalie" sort="Bastien, Nathalie" uniqKey="Bastien N" first="Nathalie" last="Bastien">Nathalie Bastien</name><affiliation wicri:level="1"><nlm:affiliation>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Kwindt, Trijntje L" sort="Kwindt, Trijntje L" uniqKey="Kwindt T" first="Trijntje L" last="Kwindt">Trijntje L. Kwindt</name><affiliation wicri:level="1"><nlm:affiliation>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia</wicri:regionArea><wicri:noRegion>British Columbia</wicri:noRegion></affiliation></author><author><name sortKey="Mahmud, Salaheddin M" sort="Mahmud, Salaheddin M" uniqKey="Mahmud S" first="Salaheddin M" last="Mahmud">Salaheddin M. Mahmud</name><affiliation wicri:level="4"><nlm:affiliation>Community Health Sciences and Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Community Health Sciences and Pharmacy, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Van Caeseele, Paul" sort="Van Caeseele, Paul" uniqKey="Van Caeseele P" first="Paul" last="Van Caeseele">Paul Van Caeseele</name><affiliation wicri:level="4"><nlm:affiliation>Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><affiliation wicri:level="4"><nlm:affiliation>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent (MeSH)</term><term>Adult (MeSH)</term><term>Aged (MeSH)</term><term>Aged, 80 and over (MeSH)</term><term>Canada (MeSH)</term><term>Case-Control Studies (MeSH)</term><term>Child (MeSH)</term><term>Child, Preschool (MeSH)</term><term>DNA, Viral (genetics)</term><term>Female (MeSH)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term><term>Humans (MeSH)</term><term>Immunization (MeSH)</term><term>Infant (MeSH)</term><term>Infant, Newborn (MeSH)</term><term>Influenza A Virus, H3N2 Subtype (genetics)</term><term>Influenza A Virus, H3N2 Subtype (immunology)</term><term>Influenza A Virus, H3N2 Subtype (isolation & purification)</term><term>Influenza Vaccines (administration & dosage)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (genetics)</term><term>Influenza, Human (immunology)</term><term>Influenza, Human (prevention & control)</term><term>Influenza, Human (virology)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Molecular Sequence Data (MeSH)</term><term>Mutation (genetics)</term><term>Protein Conformation (MeSH)</term><term>Seasons (MeSH)</term><term>Young Adult (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN viral (génétique)</term><term>Adolescent (MeSH)</term><term>Adulte (MeSH)</term><term>Adulte d'âge moyen (MeSH)</term><term>Canada (MeSH)</term><term>Conformation des protéines (MeSH)</term><term>Données de séquences moléculaires (MeSH)</term><term>Enfant (MeSH)</term><term>Enfant d'âge préscolaire (MeSH)</term><term>Femelle (MeSH)</term><term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term><term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term><term>Grippe humaine (génétique)</term><term>Grippe humaine (immunologie)</term><term>Grippe humaine (prévention et contrôle)</term><term>Grippe humaine (virologie)</term><term>Humains (MeSH)</term><term>Immunisation (MeSH)</term><term>Jeune adulte (MeSH)</term><term>Mutation (génétique)</term><term>Mâle (MeSH)</term><term>Nourrisson (MeSH)</term><term>Nouveau-né (MeSH)</term><term>Saisons (MeSH)</term><term>Sous-type H3N2 du virus de la grippe A (génétique)</term><term>Sous-type H3N2 du virus de la grippe A (immunologie)</term><term>Sous-type H3N2 du virus de la grippe A (isolement et purification)</term><term>Sujet âgé (MeSH)</term><term>Sujet âgé de 80 ans ou plus (MeSH)</term><term>Vaccins antigrippaux (administration et posologie)</term><term>Vaccins antigrippaux (immunologie)</term><term>Études cas-témoins (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Viral</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Influenza Vaccines</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Canada</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antigrippaux</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza, Human</term><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN viral</term><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Grippe humaine</term><term>Mutation</term><term>Sous-type H3N2 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Grippe humaine</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Vaccins antigrippaux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Influenza A Virus, H3N2 Subtype</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Sous-type H3N2 du virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Case-Control Studies</term><term>Child</term><term>Child, Preschool</term><term>Female</term><term>Humans</term><term>Immunization</term><term>Infant</term><term>Infant, Newborn</term><term>Male</term><term>Middle Aged</term><term>Molecular Sequence Data</term><term>Protein Conformation</term><term>Seasons</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Adulte</term><term>Adulte d'âge moyen</term><term>Canada</term><term>Conformation des protéines</term><term>Données de séquences moléculaires</term><term>Enfant</term><term>Enfant d'âge préscolaire</term><term>Femelle</term><term>Humains</term><term>Immunisation</term><term>Jeune adulte</term><term>Mâle</term><term>Nourrisson</term><term>Nouveau-né</term><term>Saisons</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Études cas-témoins</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Canada</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS/FINDINGS</b></p><p>Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24667168</PMID><DateCompleted><Year>2015</Year><Month>01</Month><Day>22</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>3</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.</ArticleTitle><Pagination><MedlinePgn>e92153</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0092153</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.</AbstractText><AbstractText Label="METHODS/FINDINGS" NlmCategory="RESULTS">Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Skowronski</LastName><ForeName>Danuta M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Janjua</LastName><ForeName>Naveed Z</ForeName><Initials>NZ</Initials><AffiliationInfo><Affiliation>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>De Serres</LastName><ForeName>Gaston</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Biological and Occupational Risks, Institut National de Santé Publique du Québec, Québec (Québec), Canada; Department of Social and Preventive Medicine, Laval University, Québec (Québec), Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sabaiduc</LastName><ForeName>Suzana</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eshaghi</LastName><ForeName>Alireza</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular Research, Public Health Ontario, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dickinson</LastName><ForeName>James A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Family Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fonseca</LastName><ForeName>Kevin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Virology, Provincial Laboratory of Public Health, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Winter</LastName><ForeName>Anne-Luise</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Communicable Disease Prevention and Control, Public Health Ontario, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gubbay</LastName><ForeName>Jonathan B</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Public Health Ontario, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology and Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Krajden</LastName><ForeName>Mel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petric</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; Clinical Prevention Services, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Charest</LastName><ForeName>Hugues</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Laboratoire de Santé Publique du Québec, Institut National de Santé Publique du Québec, Sainte-Anne-de-Bellevue, Québec, Canada; Département De Microbiologie, Infectiologie et Immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bastien</LastName><ForeName>Nathalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwindt</LastName><ForeName>Trijntje L</ForeName><Initials>TL</Initials><AffiliationInfo><Affiliation>School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mahmud</LastName><ForeName>Salaheddin M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Community Health Sciences and Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Caeseele</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Influenza and Respiratory Virus Section, National Microbiology 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IdType="pubmed">15866076</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country><region><li>Alberta</li><li>Manitoba</li><li>Ontario</li><li>Québec</li></region><settlement><li>Calgary</li><li>Québec (ville)</li><li>Toronto</li><li>Winnipeg</li></settlement><orgName><li>Université Laval</li><li>Université de Calgary</li><li>Université de Toronto</li><li>Université du Manitoba</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Skowronski, Danuta M" sort="Skowronski, Danuta M" uniqKey="Skowronski D" first="Danuta M" last="Skowronski">Danuta M. 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Mahmud</name><name sortKey="Petric, Martin" sort="Petric, Martin" uniqKey="Petric M" first="Martin" last="Petric">Martin Petric</name><name sortKey="Sabaiduc, Suzana" sort="Sabaiduc, Suzana" uniqKey="Sabaiduc S" first="Suzana" last="Sabaiduc">Suzana Sabaiduc</name><name sortKey="Van Caeseele, Paul" sort="Van Caeseele, Paul" uniqKey="Van Caeseele P" first="Paul" last="Van Caeseele">Paul Van Caeseele</name><name sortKey="Winter, Anne Luise" sort="Winter, Anne Luise" uniqKey="Winter A" first="Anne-Luise" last="Winter">Anne-Luise Winter</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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