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

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...

Full description

Bibliographic Details
Main Authors: Danuta M Skowronski, Naveed Z Janjua, Gaston De Serres, Suzana Sabaiduc, Alireza Eshaghi, James A Dickinson, Kevin Fonseca, Anne-Luise Winter, Jonathan B Gubbay, Mel Krajden, Martin Petric, Hugues Charest, Nathalie Bastien, Trijntje L Kwindt, Salaheddin M Mahmud, Paul Van Caeseele, Yan Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3965421?pdf=render
_version_ 1818286808065114112
author Danuta M Skowronski
Naveed Z Janjua
Gaston De Serres
Suzana Sabaiduc
Alireza Eshaghi
James A Dickinson
Kevin Fonseca
Anne-Luise Winter
Jonathan B Gubbay
Mel Krajden
Martin Petric
Hugues Charest
Nathalie Bastien
Trijntje L Kwindt
Salaheddin M Mahmud
Paul Van Caeseele
Yan Li
author_facet Danuta M Skowronski
Naveed Z Janjua
Gaston De Serres
Suzana Sabaiduc
Alireza Eshaghi
James A Dickinson
Kevin Fonseca
Anne-Luise Winter
Jonathan B Gubbay
Mel Krajden
Martin Petric
Hugues Charest
Nathalie Bastien
Trijntje L Kwindt
Salaheddin M Mahmud
Paul Van Caeseele
Yan Li
author_sort Danuta M Skowronski
collection DOAJ
description 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.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.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.
first_indexed 2024-12-13T01:30:28Z
format Article
id doaj.art-6ec04d279c424b7f886653fb7c6f441f
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-13T01:30:28Z
publishDate 2014-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-6ec04d279c424b7f886653fb7c6f441f2022-12-22T00:04:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9215310.1371/journal.pone.0092153Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.Danuta M SkowronskiNaveed Z JanjuaGaston De SerresSuzana SabaiducAlireza EshaghiJames A DickinsonKevin FonsecaAnne-Luise WinterJonathan B GubbayMel KrajdenMartin PetricHugues CharestNathalie BastienTrijntje L KwindtSalaheddin M MahmudPaul Van CaeseeleYan LiInfluenza 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.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.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.http://europepmc.org/articles/PMC3965421?pdf=render
spellingShingle Danuta M Skowronski
Naveed Z Janjua
Gaston De Serres
Suzana Sabaiduc
Alireza Eshaghi
James A Dickinson
Kevin Fonseca
Anne-Luise Winter
Jonathan B Gubbay
Mel Krajden
Martin Petric
Hugues Charest
Nathalie Bastien
Trijntje L Kwindt
Salaheddin M Mahmud
Paul Van Caeseele
Yan Li
Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
PLoS ONE
title Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
title_full Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
title_fullStr Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
title_full_unstemmed Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
title_short Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
title_sort low 2012 13 influenza vaccine effectiveness associated with mutation in the egg adapted h3n2 vaccine strain not antigenic drift in circulating viruses
url http://europepmc.org/articles/PMC3965421?pdf=render
work_keys_str_mv AT danutamskowronski low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT naveedzjanjua low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT gastondeserres low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT suzanasabaiduc low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT alirezaeshaghi low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT jamesadickinson low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT kevinfonseca low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT anneluisewinter low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT jonathanbgubbay low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT melkrajden low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT martinpetric low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT huguescharest low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT nathaliebastien low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT trijntjelkwindt low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT salaheddinmmahmud low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT paulvancaeseele low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses
AT yanli low201213influenzavaccineeffectivenessassociatedwithmutationintheeggadaptedh3n2vaccinestrainnotantigenicdriftincirculatingviruses