Malaria Vaccine: Pfs25-rEPA

疟疾疫苗：Pfs25-rEPA

• 批准号: 8745457
• 负责人: Patrick Duffy
• 金额: $ 336.23万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8745457
• 关键词: Alhydrogel; Antibody Formation; Antigens; Area; Carrier Proteins; Culicidae; Cyclic GMP; Drug Formulations; Malaria; Malaria Vaccines; Mali; Parasites; Phase I Clinical Trials; Pichia; Process; Proteins; Recombinants; Safety; Staging; Surface; Target Populations; Toxin; Vaccines; base; burden of illness; immunogenic; immunogenicity; mutant; transmission process; vaccine development; vaccine safety

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.

基于Pfs25的TBV开发面临的主要挑战是寻找一种具有良好安全性并能够诱导持续高抗体应答的配方。此前，LMIV已经证明，将Pfs25与铜绿假单胞菌载体蛋白ExoProtein A(EPA)偶联，大大提高了在巴斯德毕赤酵母中生产的重组Pfs25的免疫原性。开发了一种将Pfs25与REPA偶联的工艺，制备了cGMP级Pfs25-EPA偶联物，并与Alwater Gel进行了复配。一期试验在美国进行。在证明疫苗是安全的、免疫原性的，并可以诱导传播减少活性后，LMIV开始在马里进行第一阶段试验，以评估疫苗的安全性、免疫原性和目标人群的传播阻断活性。