Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.
Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.
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DOI：
10.1126/sciadv.abl5209
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发表时间：
2022-04-08
期刊：
影响因子：
13.6
通讯作者：
Valkenburg SA
中科院分区：
文献类型：
--
作者：
Bull MB;Gu H;Ma FNL;Perera LP;Poon LLM;Valkenburg SA
为了确定病毒适应T细胞应答的可能性，我们通过直接离体从感染小鼠中进行下一代测序来探测完整的流感病毒基因组，在实验性T细胞疫苗的背景下，基于H5 N1的病毒载体的牛痘疫苗Wyeth/IL-15/5 Flu，与当前的护理标准，季节性灭活流感疫苗（IIV）和未接种条件相比。Wyeth/IL-15/5 Flu疫苗接种与流感基因组中突变发生率和频率增加一致;然而，T细胞表位区域内未富集突变，但保守血凝素干细胞区域内出现高等位基因频率突变和PB 2哺乳动物适应性突变。CD 4+和CD 8 + T细胞亚群的消耗导致接种小鼠中突变体的频率降低;因此，疫苗介导的T细胞应答是病毒多样化的重要驱动因素。我们的研究结果表明，惠氏/IL-15/5流感病毒不会产生T细胞逃逸突变体，但会通过严格的瓶颈增加病毒适应的随机事件。新一代T细胞活化流感疫苗随机免疫压力大于灭活疫苗。
To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell–based vaccine, an H5N1-based viral vectored vaccinia vaccine Wyeth/IL-15/5Flu, versus the current standard-of-care, seasonal inactivated influenza vaccine (IIV) and unvaccinated conditions. Wyeth/IL-15/5Flu vaccination was coincident with increased mutation incidence and frequency across the influenza genome; however, mutations were not enriched within T cell epitope regions, but high allele frequency mutations within conserved hemagglutinin stem regions and PB2 mammalian adaptive mutations arose. Depletion of CD4+ and CD8+ T cell subsets led to reduced frequency of mutants in vaccinated mice; therefore, vaccine-mediated T cell responses were important drivers of virus diversification. Our findings suggest that Wyeth/IL-15/5Flu does not generate T cell escape mutants but increases stochastic events for virus adaptation by stringent bottlenecks. Next-generation T cell–activating influenza vaccine stochastic immune pressure is greater than inactivated vaccines.
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影响因子：
7.7
作者：
Hulme KD;Karawita AC;Pegg C;Bunte MJ;Bielefeldt-Ohmann H;Bloxham CJ;Van den Hoecke S;Setoh YX;Vrancken B;Spronken M;Steele LE;Verzele NA;Upton KR;Khromykh AA;Chew KY;Sukkar M;Phipps S;Short KR
通讯作者：
Short KR
DOI：
10.1093/cid/cis327
发表时间：
2012-07
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Lillie PJ;Berthoud TK;Powell TJ;Lambe T;Mullarkey C;Spencer AJ;Hamill M;Peng Y;Blais ME;Duncan CJ;Sheehy SH;Havelock T;Faust SN;Williams RL;Gilbert A;Oxford J;Dong T;Hill AV;Gilbert SC
通讯作者：
Gilbert SC
影响因子：
5.4
作者：
Brockman, Mark A.;Schneidewind, Arne;Allen, Todd M.
通讯作者：
Allen, Todd M.
DOI：
10.1073/pnas.1202143109
发表时间：
2012-06-19
影响因子：
11.1
作者：
Fang, Min;Siciliano, Nicholas A.;Sigal, Luis J.
通讯作者：
Sigal, Luis J.
DOI：
10.1164/rccm.201411-1988oc
发表时间：
2015-06-15
影响因子：
24.7
作者：
Hayward, Andrew C.;Wang, Lili;McMichael, Andrew J.
通讯作者：
McMichael, Andrew J.