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

被引：324

作者：

Skowronski, Danuta M. ^{[1
,2
]}

Janjua, Naveed Z. ^{[2
,3
]}

De Serres, Gaston ^{[4
,5
]}

Sabaiduc, Suzana ^{[1
]}

Eshaghi, Alireza ^{[6
]}

Dickinson, James A. ^{[7
]}

Fonseca, Kevin ^{[8
,9
]}

Winter, Anne-Luise ^{[10
]}

Gubbay, Jonathan B. ^{[11
,12
,13
,14
]}

Krajden, Mel ^{[1
,3
]}

Petric, Martin ^{[1
,3
]}

Charest, Hugues ^{[15
,16
]}

Bastien, Nathalie ^{[17
]}

Kwindt, Trijntje L. ^{[2
]}

Mahmud, Salaheddin M. ^{[18
]}

Van Caeseele, Paul ^{[19
,20
]}

Li, Yan ^{[17
,20
]}

机构：

[1] British Columbia Ctr Dis Control, Communicable Dis Prevent & Control Serv, Vancouver, BC, Canada

[2] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada

[3] British Columbia Ctr Dis Control, Clin Prevent Serv, Vancouver, BC, Canada

[4] Inst Natl Sante Publ Quebec, Dept Biol & Occupat Risks, Quebec City, PQ, Canada

[5] Univ Laval, Dept Social & Prevent Med, Quebec City, PQ, Canada

[6] Publ Hlth Ontario, Dept Mol Res, Toronto, ON, Canada

[7] Univ Calgary, Calgary, AB, Canada

[8] Prov Lab Publ Hlth, Dept Virol, Calgary, AB, Canada

[9] Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB, Canada

[10] Publ Hlth Ontario, Communicable Dis Prevent & Control, Toronto, ON, Canada

[11] Publ Hlth Ontario, Dept Microbiol, Toronto, ON, Canada

[12] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[13] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A1, Canada

[14] Hosp Sick Children, Dept Paediat, Toronto, ON M5G 1X8, Canada

[15] Inst Natl Sante Publ Quebec, Lab Sante Publ Quebec, Ste Anne De Bellevue, PQ, Canada

[16] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ H3C 3J7, Canada

[17] Natl Microbiol Lab, Influenza & Resp Virus Sect, Winnipeg, MB, Canada

[18] Univ Manitoba, Winnipeg, MB, Canada

[19] Manitoba Hlth, Cadham Prov Lab, Winnipeg, MB, Canada

[20] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada

来源：

PLOS ONE | 2014年 / 9卷 / 03期

基金：

加拿大健康研究院;

关键词：

SENTINEL SURVEILLANCE NETWORK; PANDEMIC H1N1 VACCINE; HEMAGGLUTININ; CANADA; EFFICACY; SUBSTITUTIONS; RECEPTOR; BINDING; SYSTEM; ACID;

D O I：

10.1371/journal.pone.0092153

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-vaccinelineage) 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.

引用

页数：15

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