MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
PLoS One. 2013 Apr 16;8(4):e61395. doi: 10.1371/journal.pone.0061395. Print 2013.
Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4(+) T cells specific for the circumsporozoite protein (CSP). Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and subjected to experimental P. falciparum challenge, we characterised the relationship between antibodies, CD4(+) T cell responses and protection from infection. Both anti-CSP antibody titres and CSP-specific CD4(+) T cells were identified as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32% (95% confidence interval (CI) 24%-41%) of infections. The addition of RTS,S-induced CSP-specific CD4(+) T cells was estimated to increase vaccine efficacy against infection to 40% (95% CI, 34%-48%). This protective efficacy is estimated to result from a 96.1% (95% CI, 93.4%-97.8%) reduction in the liver-to-blood parasite inoculum, indicating that in volunteers who developed P. falciparum infection, a small number of parasites (often the progeny of a single surviving sporozoite) are responsible for breakthrough blood-stage infections.
接种红细胞前期疟疾疫苗 RTS,S 可诱导高水平的针对环子孢子蛋白（CSP）的抗体和 CD4(+)T 细胞。利用受 RTS,S 疫苗接种且经疟原虫实验性攻击的疟疾初发成年人的感染生物学模型拟合数据，我们描述了抗体、CD4(+)T 细胞反应与免受感染之间的关系。抗 CSP 抗体滴度和 CSP 特异性 CD4(+)T 细胞均被确定为保护的免疫替代物，RTS,S 诱导的抗 CSP 抗体估计可预防 32%（95%置信区间（CI）24%-41%）的感染。据估计，RTS,S 诱导的 CSP 特异性 CD4(+)T 细胞的添加可使疫苗对感染的疗效提高至 40%（95%CI，34%-48%）。这种保护功效估计是由于肝脏到血液寄生虫接种量减少了 96.1%（95%CI，93.4%-97.8%），这表明在发生疟原虫感染的志愿者中，少量寄生虫（通常是单个存活的孢子虫的后代）导致了突破性的血液期感染。
