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PLoS One. 2014 Mar 25;9(3):e92153. doi: 10.1371/journal.pone.0092153. eCollection 2014.

Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.

Author information

1
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.
2
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.
3
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.
4
Communicable Disease Prevention and Control Service, British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.
5
Department of Molecular Research, Public Health Ontario, Toronto, Ontario, Canada.
6
Family Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
7
Department of Virology, Provincial Laboratory of Public Health, Calgary, Alberta, Canada; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
8
Communicable Disease Prevention and Control, Public Health Ontario, Toronto, Ontario, Canada.
9
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.
10
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.
11
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.
12
Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
13
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
14
Community Health Sciences and Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
15
Cadham Provincial Laboratory, Manitoba Health, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
16
Influenza and Respiratory Virus Section, National Microbiology Laboratory, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.

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.

PMID:
24667168
PMCID:
PMC3965421
DOI:
10.1371/journal.pone.0092153
[Indexed for MEDLINE]
Free PMC Article

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