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Cited by 416Influenza Virus Research StudiesRespiratory viral infections researchVirology and Viral Diseases

Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses

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Skowronski, Danuta M., Janjua, Naveed Z., De Serres, Gaston, Sabaiduc, Suzana, Eshaghi, Alireza, Dickinson, James A., Fonseca, Kevin, Winter, Anne-Luise +9 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0092153PMC PMC3965421
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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.

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  • Egg adaptation occurs whereby the vaccine strain of virus becomes adapted to the egg used for production, leading to key mutations that mean it is not well matched to, and does not protect against, the circulating viral strain.

    “Another issue that is increasingly recognized is egg adaptation, whereby the vaccine strain of virus becomes adapted to the egg used for production, leading to key mutations that mean it is not well matched to, and does not protect against, the circulating viral strain114.”

    From A guide to vaccinology: from basic principles to new developments (2021) · cites this paper as [114]

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Authors
Skowronski, D. M., Janjua, N. Z., De Serres, G., Sabaiduc, S., Eshaghi, A., Dickinson, J. A., Fonseca, K., Winter, A.-L., Gubbay, J. B., Krajden, M., Petric, M., Charest, H., Bastien, N., Kwindt, T. L., Mahmud, S. M., Van Caeseele, P., & Li, Y.
Affiliations
  • University of British Columbia (CA)
  • BC Centre for Disease Control (CA)
  • Public Health Ontario (CA)
  • University of Calgary (CA)
  • University of Toronto (CA)
  • Institut National de Santé Publique du Québec (CA)
  • University of Manitoba (CA)
Corresponding author
Skowronski, Danuta M.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-03-25
Volume
9
Issue
3
Pages
e92153
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0092153
PMC
PMC3965421
OpenAlex
W2043925105
Cited by
416
References
42
Citations by year
2026: 17 · 2025: 16 · 2024: 27 · 2023: 14 · 2022: 25 · 2021: 31 · 2020: 46 · 2019: 37 · 2018: 47 · 2017: 43 · 2016: 44 · 2015: 41 · 2014: 26 · 2013: 1
FWCI
38.79
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Pfizer
  • GlaxoSmithKline
  • Sanofi
  • British Columbia Centre for Disease Control
  • Sanofi Pasteur
  • Canadian Institutes of Health Research (90193_1)
  • Institute of Infection and Immunity
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
influenza vaccine effectiveness, H3N2, antigenic drift, vaccine strain mismatch, hemagglutination inhibition, antigenic determinants, influenza B, A(H1N1)pdm09
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Canada, Child, Child, Preschool, DNA, Viral, Female, Humans, Immunization, Infant, Infant, Newborn, Influenza, Human, Influenza Vaccines, Male, Middle Aged, Molecular Sequence Data, Mutation, Protein Conformation, Seasons, Case-Control Studies, Hemagglutinin Glycoproteins, Influenza Virus, Influenza A Virus, H3N2 Subtype, Young Adult

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