Virus-like particles induce robust human T-helper cell responses

Virus-like particles induce robust human T-helper cell responses
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DOI:
10.1002/eji.201142064
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发表时间:
2012-02-01
影响因子:
5.4
通讯作者:
Romero, Pedro
Romero, Pedro
中科院分区:
医学3区
文献类型:
--
作者:
Braun, Marion;Jandus, Camilla;Romero, Pedro

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在合成疫苗中,病毒样颗粒(VLP)因其诱导强体液应答的能力而被使用。尽管抗体同种型转换需要辅助性T细胞,但关于基于VLP的疫苗诱导的CD 4 + T细胞应答的报道很少。还需要进一步了解辅助性T细胞,以优化CD 8 + T细胞疫苗接种。在这里,我们分析了人CD 4 + T细胞对MelQbG 10疫苗接种的反应,MelQbG 10是一种与来自黑素瘤自身抗原Melan-A的长肽共价连接的Q β-VLP。在所有分析的患者中,我们发现主要是IgG 1和IgG 3同种型的强烈抗体应答,以及伴随的Q β特异性Th 1偏向CD 4 + T细胞应答。虽然不太强,但也发现了对Melan-A货物肽特异的相当的B-和CD 4 + T细胞应答。需要进一步优化以将响应更多地转向货物肽。然而,数据表明VLP通过建立强大的CD 4 + T细胞帮助诱导体液和细胞免疫应答的高潜力。
Among synthetic vaccines, virus-like particles (VLPs) are used for their ability to induce strong humoral responses. Very little is reported on VLP-based-vaccine-induced CD4+ T-cell responses, despite the requirement of helper T cells for antibody isotype switching. Further knowledge on helper T cells is also needed for optimization of CD8+ T-cell vaccination. Here, we analysed human CD4+ T-cell responses to vaccination with MelQbG10, which is a Q beta-VLP covalently linked to a long peptide derived from the melanoma self-antigen Melan-A. In all analysed patients, we found strong antibody responses of mainly IgG1 and IgG3 isotypes, and concomitant Th1-biased CD4+ T-cell responses specific for Q beta. Although less strong, comparable B- and CD4+ T-cell responses were also found specific for the Melan-A cargo peptide. Further optimization is required to shift the response more towards the cargo peptide. Nevertheless, the data demonstrate the high potential of VLPs for inducing humoral and cellular immune responses by mounting powerful CD4+ T-cell help.