Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
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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DOI：
10.1371/journal.pone.0092153
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Skowronski DM;Janjua NZ;De Serres G;Sabaiduc S;Eshaghi A;Dickinson JA;Fonseca K;Winter AL;Gubbay JB;Krajden M;Petric M;Charest H;Bastien N;Kwindt TL;Mahmud SM;Van Caeseele P;Li Y
流感疫苗有效性（VE）通常在疫苗与流行毒株匹配/不匹配的背景下进行解释，后者的进化漂移被用来解释保护力降低。然而，在2012-13赛季，详细的基因型和表型表征表明，低VE反而与蛋适应H3 N2疫苗株的突变有关，而不是循环病毒中的抗原漂移。在加拿大，通过检测阴性病例对照设计估计了针对经医疗护理、PCR确认的流感的特异性VE。甲型流感病毒通过已建立的血凝素（HA）抗原位点的氨基酸（AA）测序进行基因型表征，并通过血凝抑制（HI）试验进行表型表征。根据WHO推荐的细胞传代疫苗原型（A/维多利亚/361/2011）以及疫苗生产中实际使用的鸡胚适应株，对H3 N2病毒进行了表征。在总共1501名参与者中，652人（43%）检测到流感病毒。近三分之二的病毒分型/亚型为A（H3 N2）（394/626; 63%）;其余为A（H1N1）pdm 09（79/626; 13%）、B/Yamagata（98/626; 16%）或B/维多利亚（54/626; 9%）。总体而言，50%（95%CI：33-63%）的次优VE是由主要的H3 N2活性驱动的，其中VE为41%（95%CI：17-59%）。所有H3 N2田间分离株均被HI表征为与WHO推荐的A/维多利亚/361/2011原型良好匹配，而除一株外，所有分离株均与疫苗生产中实际使用的鸡胚适应株在抗原性上不同。蛋适应菌株本身在抗原性上不同于WHO推荐的原型，并且在抗原位点B [H156 Q，G186 V]和D [S219 Y]处具有三个AA突变。相反，循环病毒在这些位置与世卫组织推荐的原型相同，具有不影响抗原性的其他遗传变异。抗A（H1N1）pdm 09的VE为59%（95%CI：16-80%），抗B/Yamagata（疫苗谱系）的VE为67%（95%CI：30-85%），抗B/维多利亚（非疫苗谱系）的VE为75%（95%CI：29-91%）。这些发现强调了监测疫苗病毒和流行毒株以解释疫苗性能的必要性。循环病毒的进化漂移无法调节，但作为基于蛋的疫苗生产的一部分引入的有影响力的突变可能会得到改进。
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.
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影响因子：
6.4
作者：
Janjua, Naveed Z.;Skowronski, Danuta M.;Petric, Martin
通讯作者：
Petric, Martin
影响因子：
5.5
作者：
Irving, Stephanie A.;Donahue, James G.;Belongia, Edward A.
通讯作者：
Belongia, Edward A.
影响因子：
6.4
作者：
KATZ, JM;WEBSTER, RG
通讯作者：
WEBSTER, RG
DOI：
10.1098/rstb.2001.1001
发表时间：
2001-12-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Brownlee, GG;Fodor, E
通讯作者：
Fodor, E
影响因子：
3.7
作者：
Jin, H;Zhou, H;Kemble, G
通讯作者：
Kemble, G