Comparing human T cell and NK cell responses in viral-based malaria vaccine trials
Comparing human T cell and NK cell responses in viral-based malaria vaccine trials
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DOI：
10.1016/j.vaccine.2009.09.132
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发表时间：
2009-12-10
期刊：
影响因子：
5.5
通讯作者：
Todryk, Stephen M.
中科院分区：
文献类型：
--
作者：
Berthoud, Tamara K.;Fletcher, Helen;Todryk, Stephen M.
以病毒为基础的疫苗接种仍然有望预防疟疾，而抗原特异性T细胞反应被认为是这种方法的主要目标，即诱导的NK细胞作为抗疟疾效应细胞的作用。或者在塑造T细胞反应方面，受到的关注较少。在这项研究中，幼稚的人类志愿者接种了由重组病毒载体鸡痘(FP9)和编码肝期抗原的改良安卡拉牛痘(MVA)或病毒体疫苗组成的加强免疫方案。干扰素-γELISPOT和细胞内细胞因子染色(ICS)显示对载体疫苗抗原有显著的T细胞反应，细胞内细胞因子染色(ICS)与随后攻击CD56(Bright)后的寄生虫血症时间增加有关，接种后淋巴细胞显著增加，CD3(+)CD56(+)淋巴细胞也增加，而CD56(DIM)细胞没有这种增加。病毒载体在体外可以有效地感染APC，但不能感染淋巴细胞，并刺激炎性细胞因子，如I型干扰素。在这些疫苗接种方案中，检测抗原特异性T细胞比NK细胞更有意义(C)2009爱思唯尔有限公司版权所有
Vaccination with viral-based vaccines continues to hold promise for the prevention of malaria Whilst antigen-specific T cell responses are considered a major aim Of Such an approach, a role for induced NK cells as anti-malarial effector cells. or in shaping T cell responses, has received less attention. In this Study naive human volunteers were vaccinated in a prime-boost vaccination regimen comprising recombinant viral vectors fowlpox (FP9) and modified vaccinia Ankara (MVA) encoding liver-stage antigens, or a virosome vaccine. Significant T cell responses specific for the vectored vaccine antigens were demonstrated by IFN gamma ELISPOT and intracellular cytokine staining (ICS) for IFN gamma and IL-2, the ICS being associated with increased time to parasitaemia following subsequent challenge Numbers of CD56(bright), lymphocytes increased significantly following vaccination, as did CD3(+) CD56(+), lymphocytes, whilst CD56(dim) cells did not No Such increases were seen with the virosome vaccine There was no significant correlation of these CD56(+) populations with the antigen-specific T cell responses nor time to parasitaemia To investigate pathways of immune activation that could contribute to these lymphocyte responses, viral vectors were shown in vitro to efficiently infect APCs but not lymphocytes, and stimulated inflammatory cytokines Such as type I interferons In conclusion. measuring antigen-specific T cells is more meaningful than NK cells in these vaccination regimens (C) 2009 Elsevier Ltd All rights reserved