T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children
T Cell Responses to the RTS,S/AS01E and RTS,S/AS02D Malaria Candidate Vaccines Administered According to Different Schedules to Ghanaian Children
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DOI：
10.1371/journal.pone.0018891
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发表时间：
2011-04-27
期刊：
影响因子：
3.7
通讯作者：
Owusu-Agyei, Seth
中科院分区：
文献类型：
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作者：
Ansong, Daniel;Asante, Kwaku P.;Owusu-Agyei, Seth
工作背景：正在开发恶性疟原虫红细胞前期候选疫苗RTS，S，以保护撒哈拉以南非洲的幼儿免受疟疾的侵害。与基于脂质体的佐剂AS 01（E）或基于水包油的佐剂AS 02（D）一起配制的RTS，S诱导恶性疟原虫环子孢子（CSP）抗原特异性抗体和T细胞应答，这与成人实验性疟疾攻击模型中的保护相关。本研究旨在评价三种疫苗接种方案在19个月期间诱导的安全性和免疫原性在加纳的两个研究中心，对5-17个月的儿童进行RTS，S/AS 01（E）和RTS，S/AS 02（D）（0，1-，0，1，2-和0，1，7-个月）。结果：RTS、S/AS 01（E）诱导的CSP特异性CD 4 T细胞产生IL-2、TNF-α和IFN-γ，并经全血抗原刺激后，细胞内细胞因子染色显示CSP特异性CD 4 T细胞产生IL-2、TNF-α和IFN-γ。与0、1或0、1、2个月的免疫方案相比，0、1、7个月的免疫方案诱导了更高的T细胞应答。与RTS，S/AS 02（D）相比，RTS，S/AS 01（E）在0、1、7个月给药时诱导更高的CD 4 T细胞应答。结论：这些结果支持RTS，S/AS 01（E）的进一步III期评价。目前正在评估免疫效应物和免疫接种时间表对疫苗保护的作用。
Background: The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS, S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS, S formulated with the liposome based adjuvant AS01(E) or the oil-in-water based adjuvant AS02(D) induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults.Methods: This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2-and 0,1,7-month) of RTS, S/AS01(E) and RTS, S/AS02(D) in children aged 5-17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites.Results: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS, S/AS01(E) induced CSP specific CD4 T cells producing IL-2, TNF-alpha, and IFN-gamma. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1-or 0,1,2-month schedule. RTS, S/AS01(E) induced higher CD4 T cell responses as compared to RTS, S/AS02(D) when given on a 0,1,7-month schedule.Conclusions: These findings support further Phase III evaluation of RTS, S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation.