Malaria Vaccine: Pfs25-rEPA

基于pfs25的TBV开发面临的主要挑战是找到一种具有高度安全性并能够诱导持续高抗体反应的配方。此前LMIV已经证明，将Pfs25与铜绿假单胞菌的载体蛋白ExoProtein A （EPA）结合，可以大大提高毕赤酵母中产生的重组Pfs25的免疫原性。研究了Pfs25与rEPA的偶联工艺，制备了cgmp级Pfs25- epa偶联物，并与醛水凝胶进行了配制。在美国进行了一期临床试验。在证明疫苗是安全的、免疫原性的，并且可以诱导减少传播活性后，LMIV在马里开始了一项一期试验，以评估疫苗在目标人群中的安全性、免疫原性和传播阻断活性。

The major challenge facing Pfs25-based TBV development is to find a formulation with great safety profile and capable of inducing sustained high antibody responses. Previously the LMIV has demonstrated that conjugating Pfs25 with carrier protein ExoProtein A (EPA) of Psuedomonas aeruginosa greatly enhance the immunogenicity of the recombinant Pfs25 produced in Pichia pastoris. A process was developed to conjugate Pfs25 with rEPA, and cGMP-grade Pfs25-EPA conjugate was manufactured and formulated with Alhydrogel. A Phase 1 trial was conducted in US. After demonstrating that vaccine was safe, immunogenic, and could induce transmission reducing activity, LMIV began a Phase 1 trial in Mali, to evaluate the vaccine safety, immunogenicity, and transmission blocking activity in target population.