Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria
Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria
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DOI：
10.4161/hv.6.1.10396
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Sim, B. Kim Lee
中科院分区：
文献类型：
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作者：
Hoffman, Stephen L.;Billingsley, Peter F.;Sim, B. Kim Lee
如果使用足够数量的免疫叮咬期和子孢子感染的蚊子，通过携带辐射减毒恶性疟原虫子孢子的蚊子叮咬对志愿者进行免疫接种，可以保护90%以上的志愿者免受疟疾的侵害。尽管如此，直到最近，人们还认为不可能开发、许可和商业化活的完整寄生虫恶性疟原虫子孢子（PfSPZ）疫苗。2003年，Sanaria的科学家重新评估了一种代谢活性、非复制型PfSPZ疫苗的潜在影响，并概述了生产这种疫苗的挑战。六年后，在克服这些挑战方面取得了重大进展。这一进展使得第一代代谢活性、非复制型PfSPZ疫苗Sanaria（TM）PfSPZ疫苗的多个临床批次得以生产和放行，成功向美国食品药品监督管理局提交了新药研究申请，并在美国马里兰州的志愿者中开始了安全性、免疫原性和保护效力研究。目前的工作重点是如何最好地提交成功的生物制品许可证申请，并在尽可能短的时间内将疫苗介绍给非洲儿童的主要目标人群。这将需要实施系统、有效的临床开发计划。短期挑战包括优化（1）生产工艺和质量控制测定的效率和规模，（2）给药方案和给药方法，（3）疫苗效力，以及（4）将疫苗递送给最需要的人的物流，并最终确定疫苗稳定和减毒的方法。中期目标是设计和建立一个生产高效稳定疫苗的设施，用于关键的3期研究和商业上市。
Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria (TM) PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, ( 3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.