T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization.
T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization.
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DOI：
10.1016/j.chom.2011.01.007
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发表时间：
2011-02-17
影响因子：
30.3
通讯作者：
Malley R
中科院分区：
文献类型：
--
作者：
Moffitt KL;Gierahn TM;Lu YJ;Gouveia P;Alderson M;Flechtner JB;Higgins DE;Malley R
肺炎链球菌是幼儿死亡的主要原因。虽然已有成功的结合多糖疫苗，但一种较便宜的不依赖血清型的基于蛋白质的肺炎球菌疫苗为预防危及生命的肺炎球菌感染提供了重大进展，特别是在发展中国家。分泌il - 17a的CD4+ T细胞（TH17）介导包括肺炎链球菌在内的多种病原体对粘膜定植的抗性。筛选了一个包含bb0.96%预测肺炎球菌蛋白的表达文库，我们从免疫肺炎球菌定植的小鼠中鉴定了TH17细胞识别的抗原。鉴定出的抗原还能诱导定植的小鼠脾细胞和人脾细胞分泌IL-17A，这表明在自然暴露过程中也会引发类似的反应。对两种已鉴定抗原的小鼠株进行免疫接种，可保护小鼠免受肺炎球菌定植，而用阻断CD4或IL-17A抗体治疗的小鼠的定植能力显著降低。这项工作证明了蛋白质组学筛选方法的潜力，通过利用th17介导的免疫来识别特定抗原，设计针对粘膜病原体的亚单位疫苗。
Streptococcus pneumoniae is a leading cause of mortality in young children. While successful conjugate polysaccharide vaccines exist, a less expensive serotype-independent protein-based pneumococcal vaccine offers a major advancement for preventing life-threatening pneumococcal infections, particularly in developing nations. IL-17A-secreting CD4+ T cells (TH17) mediate resistance to mucosal colonization by multiple pathogens including S. pneumoniae. Screening an expression library containing >96% of predicted pneumococcal proteins, we identified antigens recognized by TH17 cells from mice immune to pneumococcal colonization. The identified antigens also elicited IL-17A secretion from colonized mouse splenocytes and human PBMCs suggesting that similar responses are primed during natural exposure. Immunization of two mouse strains with identified antigens provided protection from pneumococcal colonization that was significantly diminished in animals treated with blocking CD4 or IL-17A antibodies. This work demonstrates the potential of proteomic screening approaches to identify specific antigens for the design of subunit vaccines against mucosal pathogens via harnessing TH17-mediated immunity.
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影响因子：
--
作者：
Zhang, Xia;Goncalves, Ricardo;Mosser, David M
通讯作者：
Mosser, David M
白介素17a介导获得的对肺炎球菌定殖的免疫力。
影响因子：
6.7
作者：
Lu, Ying-Jie;Gross, Jane;Bogaert, Debby;Finn, Adam;Bagrade, Linda;Zhang, Qibo;Kolls, Jay K.;Srivastava, Amit;Lundgren, Anna;Forte, Sophie;Thompson, Claudette M.;Harney, Kathleen F.;Anderson, Porter W.;Lipsitch, Marc;Malley, Richard
通讯作者：
Malley, Richard
影响因子：
3.1
作者：
PATON, JC;LOCK, RA;BOULNOIS, GJ
通讯作者：
BOULNOIS, GJ
影响因子：
3.1
作者：
Glover, David T.;Hollingshead, Susan K.;Briles, David E.
通讯作者：
Briles, David E.
DOI：
10.1073/pnas.0501254102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Malley, R;Trzcinski, K;Lipsitch, M
通讯作者：
Lipsitch, M