Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-γ
Protective immunity induced with malaria vaccine, RTS,S, is linked to Plasmodium falciparum circumsporozoite protein-specific CD4+ and CD8+ T cells producing IFN-γ
复制标题
DOI：
10.4049/jimmunol.171.12.6961
复制
发表时间：
2003-12-15
影响因子：
4.4
通讯作者：
Krzych, U
中科院分区：
文献类型：
--
作者：
Sun, PF;Schwenk, R;Krzych, U
恶性疟原虫环子孢子（CS）蛋白为基础的红细胞前期疫苗，RTS，S，诱导对实验性子孢子攻击的高水平的保护。构成保护的免疫机制仅被部分理解，但推测依赖于抗体和T细胞应答。在本研究中，我们比较了CS蛋白肽回忆IFN-γ反应性的前和RTS，S免疫淋巴细胞从20名受试者接种RTS，S。我们观察到受RTS，S保护的受试者IFN-γ升高;此外，CD 4（+）和CD 8（+）T细胞均响应CS蛋白肽产生IFN-γ。值得注意的是，尽管仅在7名受试者中的2名中观察到，但持久的保护与持续的IFN-γ应答相关。这是第一项研究证明了在控制疟原虫子孢子攻击研究中重组疟疾疫苗诱导的保护与Ag特异性T细胞应答之间的相关性。基于实地的疟疾疫苗研究正在进行中，以验证这种细胞反应的建立，作为对红细胞外期疟疾疫苗的保护性免疫的可能的体外相关性。
The Plasmodium falciparum circumsporozoite (CS) protein-based pre-erythrocytic stage vaccine, RTS,S, induces a high level of protection against experimental sporozoite challenge. The immune mechanisms that constitute protection are only partially understood, but are presumed to rely on Abs and T cell responses. In the present study we compared CS protein peptide-recalled IFN-gamma reactivity of pre- and RTS,S-immune lymphocytes from 20 subjects vaccinated with RTS,S. We observed elevated IFN-gamma in subjects protected by RTS,S; moreover, both CD4(+) and CD8(+) T cells produced IFN-gamma in response to CS protein peptides. Significantly, protracted protection, albeit observed only in two of seven subjects, was associated with sustained IFN-gamma response. This is the first study demonstrating correlation in a controlled Plasmodia sporozoite challenge study between protection induced by a recombinant malaria vaccine and Ag-specific T cell responses. Field-based malaria vaccine studies are in progress to validate the establishment of this cellular response as a possible in vitro correlate of protective immunity to exo-erythrocytic stage malaria vaccines.