a GSK Vaccines , Rixensart , Belgium.
Hum Vaccin Immunother. 2018 Jan 2;14(1):17-27. doi: 10.1080/21645515.2017.1381809. Epub 2017 Dec 1.
The candidate malaria vaccine RTS,S has demonstrated 45.7% efficacy over 18 months against all clinical disease in a phase-III field study of African children. RTS,S targets the circumsporozoite protein (CSP), which is expressed on the Plasmodium sporozoite during the pre-erythrocyte stage of its life-cycle; the stage between mosquito bite and liver infection. Early in the development of RTS,S, it was recognized that CSP-specific cell-mediated immunity (CMI) was required to complement CSP-specific antibody-mediated immunity. In reviewing RTS,S clinical studies, associations between protection and various types of CMI (CSP-specific CD4 T cells and INF-γ ELISPOTs) have been identified, but not consistently. It is plausible that certain CD4 T cells support antibody responses or co-operate with other immune-cell types to potentially elicit protection. However, the identities of vaccine correlates of protection, implicating either CSP-specific antibodies or T cells remain elusive, suggesting that RTS,S clinical trials may benefit from additional immunogenicity analyses that can be informed by the results of controlled human malaria infection studies.
候选疟疾疫苗 RTS,S 在一项针对非洲儿童的 III 期现场研究中，在 18 个月的时间里对所有临床疾病的有效率为 45.7%。RTS,S 针对环子孢子蛋白（CSP），该蛋白在疟原虫的子孢子期在其生命周期的红细胞前阶段表达; 这是蚊子叮咬和肝脏感染之间的阶段。在 RTS,S 的早期开发中，人们认识到 CSP 特异性细胞介导的免疫（CMI）是补充 CSP 特异性抗体介导的免疫所必需的。在回顾 RTS,S 的临床研究时，已经确定了保护与各种类型的 CMI（CSP 特异性 CD4 T 细胞和 INF-γ ELISPOT）之间的关联，但并非始终如此。某些 CD4 T 细胞可能支持抗体反应或与其他免疫细胞类型合作，以潜在地引发保护作用，这是合理的。然而，疫苗保护的相关性的特征，涉及到 CSP 特异性抗体或 T 细胞仍然难以捉摸，这表明 RTS,S 临床试验可能受益于额外的免疫原性分析，这些分析可以通过受控的人体疟疾感染研究的结果来提供信息。
