Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013.
Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013.
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DOI：
10.1093/cid/ciy097
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发表时间：
2018-07-18
期刊：
影响因子：
--
通讯作者：
Grad YH
中科院分区：
文献类型：
--
作者：
Cobey S;Gouma S;Parkhouse K;Chambers BS;Ertl HC;Schmader KE;Halpin RA;Lin X;Stockwell TB;Das SR;Landon E;Tesic V;Youngster I;Pinsky BA;Wentworth DE;Hensley SE;Grad YH
流感疫苗接种的目的是预防感染流感病毒，降低相关的发病率和死亡率；然而，疫苗的效力可能不大，特别是对A亚型(H3N2)。低VE被归因于疫苗和流行流感毒株之间的不匹配，以及疫苗仅在人群中的一小部分引发保护性免疫。2012-2013年季节H3N2VE较低是由于鸡蛋适应性突变造成实际疫苗毒株(IVR-165)与预期疫苗毒株(A/Victoria/361/2011)和主要流通毒株(分支3C.2和3C.3)之间的抗原不匹配。我们调查了2012-2013年低VE的基础，方法是确定接种和未接种疫苗的人是否感染了不同的病毒株，并评估了接种前后成人队列中IVR-165、A/Victoria/361/2011和3C.2和3C.3株的血清学反应。我们发现，感染接种疫苗和未接种疫苗的个体的菌株之间没有显著的遗传差异。接种疫苗提高了A/Victoria/361/2011和3C.2和3C.3代表菌株的滴度，与IVR-165的滴度一样高。这些结果与假设一致，即接种疫苗增强了交叉反应免疫反应，而不是针对独特疫苗表位的特定反应。只有大约三分之一的队列实现了≥滴度4倍的增加。与基于雪貂研究的分析相反，2012-2013年成人H3N2VE降低似乎并不是由于疫苗毒株的卵子适应。相反，低VE可能是由于部分人群中疫苗免疫原性低所致。2012-2013年H3N2疫苗的低效力似乎是由于疫苗在一小部分成年人中的低免疫原性，而不是由于诱导了对先前在免疫幼稚雪貂身上进行的试验所建议的鸡蛋适应株的狭义、特异性反应。
Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine’s elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012–2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). We investigated the basis of low VE in 2012–2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. In contrast to analyses based on ferret studies, low H3N2 VE in 2012–2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population. Low H3N2 vaccine effectiveness in 2012–2013 appears attributable to low vaccine immunogenicity in a subset of adults, and not the induction of a narrow, specific response to the egg-adapted strain suggested by previous experiments in immunologically naive ferrets.
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DOI：
10.1093/bioinformatics/btx610
发表时间：
2018-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Hadfield J;Croucher NJ;Goater RJ;Abudahab K;Aanensen DM;Harris SR
通讯作者：
Harris SR
DOI：
10.1084/jem.20130212
发表时间：
2013-07-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li Y;Myers JL;Bostick DL;Sullivan CB;Madara J;Linderman SL;Liu Q;Carter DM;Wrammert J;Esposito S;Principi N;Plotkin JB;Ross TM;Ahmed R;Wilson PC;Hensley SE
通讯作者：
Hensley SE
影响因子：
6.4
作者：
Flannery, Brendan;Zimmerman, Richard K.;Fry, Alicia M.
通讯作者：
Fry, Alicia M.
关于原始抗原罪的歧视。 ii。较低生物的证明。
DOI：
10.1084/jem.124.3.347
发表时间：
1966-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fazekas de St Groth;Webster RG
通讯作者：
Webster RG
影响因子：
82.9
作者：
Lee J;Boutz DR;Chromikova V;Joyce MG;Vollmers C;Leung K;Horton AP;DeKosky BJ;Lee CH;Lavinder JJ;Murrin EM;Chrysostomou C;Hoi KH;Tsybovsky Y;Thomas PV;Druz A;Zhang B;Zhang Y;Wang L;Kong WP;Park D;Popova LI;Dekker CL;Davis MM;Carter CE;Ross TM;Ellington AD;Wilson PC;Marcotte EM;Mascola JR;Ippolito GC;Krammer F;Quake SR;Kwong PD;Georgiou G
通讯作者：
Georgiou G