Centre for Geographical Medical Research, Kenya Medical Research Institute, Kilifi, Kenya.
PLoS One. 2009 Dec 23;4(12):e8434. doi: 10.1371/journal.pone.0008434.
The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and regulatory T-cells determines the outcome of an infection. As Malaria parasites have been shown to induce immunosuppressive responses to the parasite and non-related antigens this study examined T-cell mediated pro-inflammatory and regulatory immune responses induced by malaria vaccination in children in an endemic area to determine if these responses were associated with vaccine immunogenicity.
Using real-time RT- PCR we profiled the expression of a panel of key markers of immunogenecity at different time points after vaccination with two viral vector vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP) or following rabies vaccination as a control.
The vaccine induced modest levels of IFN-gamma mRNA one week after vaccination. There was also an increase in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in the FFM ME-TRAP vaccine group; however, this may have been driven by natural exposure to parasite rather than by vaccination.
Quantitative PCR is a useful method for evaluating vaccine induced cell mediated immune responses in frozen PBMC from children in a malaria endemic country. Future studies should seek to use vaccine vectors that increase the magnitude and quality of the IFN-gamma immune response in naturally exposed populations and should monitor the induction of a regulatory T cell response.
T 细胞介导的免疫反应在自然感染或接种疫苗后控制疟疾方面起着核心作用。越来越多的证据表明,T 细胞反应具有异质性,免疫反应的质量以及促炎和调节性 T 细胞之间的平衡决定了感染的结果。由于疟疾寄生虫已被证明会诱导针对寄生虫和非相关抗原的免疫抑制反应,因此本研究检查了在流行地区接种疟疾疫苗后儿童中由疟疾引起的 T 细胞介导的促炎和调节性免疫反应,以确定这些反应是否与疫苗免疫原性相关。
使用实时 RT-PCR,我们在接种两种表达疟疾 TRAP 抗原的病毒载体疫苗(FP9-TRAP 和 MVA-TRAP)或接种狂犬病疫苗作为对照后不同时间点,对一组关键免疫原性标志物的表达进行了分析。
疫苗接种后一周诱导出适度水平的 IFN-γ mRNA。在 FFM ME-TRAP 疫苗组中,TRAP 刺激和培养基刺激的细胞中 FoxP3 mRNA 的表达也增加;然而,这可能是由对寄生虫的自然暴露而不是由疫苗接种引起的。
定量 PCR 是评估疟疾流行国家儿童冷冻 PBMC 中疫苗诱导的细胞介导免疫反应的有用方法。未来的研究应寻求使用可增加自然暴露人群中 IFN-γ 免疫反应的幅度和质量的疫苗载体,并应监测调节性 T 细胞反应的诱导。