Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever.
Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever.
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DOI：
10.3389/fimmu.2017.01276
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发表时间：
2017
影响因子：
7.3
通讯作者：
Pollard AJ
中科院分区：
文献类型：
--
作者：
Blohmke CJ;Hill J;Darton TC;Carvalho-Burger M;Eustace A;Jones C;Schreiber F;Goodier MR;Dougan G;Nakaya HI;Pollard AJ
人们对口服减毒活疫苗预防伤寒的机制知之甚少。在这里，我们分析了用Ty21a或疫苗候选物M01ZH09接种后的转录应答。反应谱的改变与疫苗诱导的免疫反应和野生型伤寒沙门氏菌攻击后的后续结果有关。尽管有广泛的遗传相似性，但我们检测到对每种疫苗的转录反应存在差异。M01 ZH09疫苗接种后7天，发现明显的细胞周期激活，并与体液免疫原性相关。相比之下，Ty21 a疫苗接种与NK细胞活性相关，并在外周血单核细胞刺激试验中得到验证，证实了NK细胞应答的上级诱导。此外，Ty21a受体中氨基酸代谢的转录特征与抗感染保护相关，包括增加孵育时间和降低严重程度。我们的数据提供了对伤寒疫苗的分子免疫应答的详细了解，这可以帮助合理设计针对肠道病原体的改进的口服减毒活疫苗。
The mechanisms by which oral, live-attenuated vaccines protect against typhoid fever are poorly understood. Here, we analyze transcriptional responses after vaccination with Ty21a or vaccine candidate, M01ZH09. Alterations in response profiles were related to vaccine-induced immune responses and subsequent outcome after wild-type Salmonella Typhi challenge. Despite broad genetic similarity, we detected differences in transcriptional responses to each vaccine. Seven days after M01ZH09 vaccination, marked cell cycle activation was identified and associated with humoral immunogenicity. By contrast, vaccination with Ty21a was associated with NK cell activity and validated in peripheral blood mononuclear cell stimulation assays confirming superior induction of an NK cell response. Moreover, transcriptional signatures of amino acid metabolism in Ty21a recipients were associated with protection against infection, including increased incubation time and decreased severity. Our data provide detailed insight into molecular immune responses to typhoid vaccines, which could aid the rational design of improved oral, live-attenuated vaccines against enteric pathogens.
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DOI：
10.4049/jimmunol.0903357
发表时间：
2010-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hall LJ;Clare S;Dougan G
通讯作者：
Dougan G
影响因子：
6.7
作者：
de Jong HK;Parry CM;van der Poll T;Wiersinga WJ
通讯作者：
Wiersinga WJ
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.5
作者：
Ip, Joanna Y.;Tong, Alan;Lynch, Kristen W.
通讯作者：
Lynch, Kristen W.
DOI：
10.1073/pnas.1621489114
发表时间：
2017-02-28
影响因子：
11.1
作者：
Kazmin, Dmitri;Nakaya, Helder I.;Pulendran, Bali
通讯作者：
Pulendran, Bali