Development of Pre-Erythrocytic Malaria Vaccines and antibodies

今年的主要发现如下。 1.完成了在肯尼亚5-12个月婴儿中进行的第二阶段临床试验的免疫和功效分析，以评估通过静脉注射途径给予经辐照的PfSPZ是否安全，并赋予持久的免疫力和对自然暴露的保护。 2.通过在Fc区引入LS突变增加mAb CIS 43的半衰期。显示CIS 43 LS在体内具有与CIS 43相当的保护作用，但在非人灵长类动物中具有显著更长的半衰期。 2.启动了针对PfCSP连接区的mAB CIS 43 LS的I期临床试验，以评估安全性、药代动力学和对受控人类疟疾感染的保护。 4.分离了一种新的人单克隆抗体L9，其定义了一个新的独特的表位，包括PfCSP的次要和主要重复序列。 5. L9针对许多抗CSP的人mAb的体内效力的比较分析。阐明了这些抗体的体内机制，表明其中几种抗体限制了肝脏中的感染。 6.开发了体内成像技术，以模拟抗体与小鼠子孢子之间的相互作用。 7.完成了L9 LS在人体中的I期安全性和疗效研究。数据显示SC或IV途径低剂量的高水平保护。 8.在马里和肯尼亚启动了两项针对婴儿和儿童的2期临床试验，以评估L9 LS对季节性和常年性感染的安全性和有效性。

The major discovery this year are as follows. 1. Completed immune and efficacy analysis of a phase II clinical trial in Kenya in 5-12 month infants to assess whether irradiated PfSPZ given by the IV route is safe, and confers durable immunity and protection against natural exposure. 2. Increased the half-life of mAb CIS43 by introducing an LS mutation in the Fc region. CIS43LS was shown to have comparable protection in vivo as CIS43 but have significantly longer half-life in non-human primates. 2. Initiated a Phase I clinical trial for mAB CIS 43LS against the junctional region of PfCSP for safety, pharmacokinetics and protection against controlled human malaria infection. 4. Isolated a new human mAb, L9, which defined a new distinct epitope comprising the minor and major repeats of PfCSP. 5. Comparative analysis of the in vivo potency of L9 against a number of human mAbs against CSP. Elucidated in vivo mechanisms of these antibodies demonstrating that several of them limit infection in the liver. 6. Developed in vivo imaging techniques to model the interaction between antibodies and sporozoites in mice. 7. Completed a Phase 1 safety and efficacy study with L9LS in humans. Data showed high level protection at low doses by SC or IV route. 8. Initiated two Phase 2 clinical trials in Mali and Kenya in infants and children to assess the safety and efficacy of L9LS against seasonal and perennial infection.