Priming with SARS CoV S DNA and boosting with SARS CoV S epitopes specific for CD4+ and CD8+ T cells promote cellular immune responses.

Priming with SARS CoV S DNA and boosting with SARS CoV S epitopes specific for CD4+ and CD8+ T cells promote cellular immune responses.
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DOI:
10.1016/j.vaccine.2007.06.047
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发表时间:
2007-09-28
期刊:
影响因子:
5.5
通讯作者:
Wu C
Wu C
中科院分区:
医学3区
文献类型:
--
作者:
Huang J;Cao Y;Du J;Bu X;Ma R;Wu C

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细胞免疫应答在抗病毒免疫中起重要作用。在我们以前的研究中,严重急性呼吸综合征冠状病毒(SARS CoV)刺突(S)DNA疫苗免疫小鼠可以诱导体液和细胞免疫应答的整个重叠的S肽池。SARS冠状病毒S蛋白T细胞功能优势表位的鉴定对于进一步了解SARS冠状病毒S DNA疫苗诱导的细胞免疫应答具有重要意义。本研究用SARS CoV S DNA疫苗免疫小鼠。随后,扫描作为免疫原的17-19聚体重叠的SARS CoV S肽库,以鉴定T细胞的特异性表位。两个H-2d限制性CD 4 + T表位,N60(S435-444)和P152(S1111-1127)和两个H-2d限制性CD 8 + T细胞表位,N50(S365-374)和P141(S1031-1047)进行了鉴定,采用酶联免疫吸附试验(ELISA)、酶联免疫斑点试验(ELISPOT)和荧光激活细胞分选仪(FACS)。SARS冠状病毒S蛋白的受体结合域(RBD)上存在CD 4 + T细胞表位(N60)和CD 8 + T细胞表位(N50),主要介导病毒与易感细胞的结合和融合。重要的是,我们的新发现是,用SARS S DNA疫苗致敏并用T细胞表位(N50和N60)加强免疫的小鼠可以促进抗原特异性CD 4+和CD 8 + T细胞免疫应答。我们的研究为SARS研究疫苗的设计提供了有价值的信息。
Cellular immune response plays an important role in antiviral immunity. In our previous study, immunization of mice with severe acute respiratory syndrome coronavirus (SARS CoV) spike (S) DNA vaccine could induce both humoral and cellular immunity in response to a pool of entire overlapping S peptides. Identification of functional dominant epitopes in SARS CoV S protein for T cells is crucial for further understanding of cellular immune responses elicited by SARS CoV S DNA vaccine. In present study, mice were immunized with SARS CoV S DNA vaccine. Subsequently, a pool of 17–19 mers overlapped SARS CoV S peptides, which served as immunogens, were scanned to identify the specific epitopes for T cells. Two H-2d restricted CD4+ T epitopes, N60 (S435–444) and P152 (S1111–1127), and two H-2d restricted CD8+ T cell epitopes, N50 (S365–374) and P141 (S1031–1047) were identified by three different methods, enzyme-linked immunosorbent assay (ELISA), enzyme linked immunospot assay (ELISPOT) and fluorescence activated cell sorter (FACS). The dominant CD4+ T cell epitope (N60) and CD8+ T cell epitope (N50) located in the receptor-binding domain (RBD) of SARS CoV S protein, which mediated virus combining and fusing to susceptible cells. Importantly, our novel finding is that mice primed with SARS S DNA vaccine and boosted with T cell epitopes (N50 and N60) could promote antigen specific CD4+ and CD8+ T cell immune responses. Our study provides valuable information for the design of vaccine for SARS study.
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DOI: 10.1016/j.micinf.2006.05.008
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