The Completion of CMC Development and Production of Pilot-Scale cGMP Lots of VLPM01, a Malaria Vaccine Candidate
Abstract
Malaria remains one of the world s most devastating infectious tropical diseases with no Food and Drug Administration (FDA)-approved vaccine to date. Malaria is caused by parasites that are transmitted to people through the bites of infected mosquitoes and results in high fevers, shaking chills, flu-like symptoms, and anemia. It is endemic mostly to Africa, Asia, and the Americas. An estimated 3.3 billion people, almost half of the world s population, are at risk of malaria. The World Health Organization (WHO) estimates malaria caused 198 million clinical episodes and 584,000 deaths worldwide in 2013. Malaria s presence and impact on nations where it is endemic is so pervasive that it has been estimated to obstruct economic growth by 1.3% annually, which over time can impact their entire gross domestic product due to lost worker productivity, discouragement of foreign investment and travel, reduced agriculture output, and impaired childhood learning. Currently, malaria is evaded with personal protective measures most often in combination with one of a number of different oral prevention medications. Medications require daily dosing prior to and during exposure, and the use of these drugs can also cause a number of uncomfortable side effects. While the use of oral medications can be effective, the emergence of drug-resistant strains to the drugs is pressing the need for more effective, durable measures such as vaccines. Malaria has also remained a scourge among military personnel since the Revolutionary War. More Soldiers have been casualties of malaria than to enemy fire in every 20th century war that has taken place in malaria-endemic regions. The last six of seven US deployments were to malaria-infested regions including Afghanistan, Iraq, and Liberia. Because of the tropical climate of Liberia, where malaria is endemic, nearly a third of all US marines and military personnel stationed there contract the parasite. As such, an effective vaccine would free theatre operations from the logistical and financial burden of drug supply lines, drug administration, management of drug-related toxicity, malaria diagnosis and treatment, evacuation and post-deployment costs. The ideal malaria vaccine would induce immunity by blocking early stages of transmission by infected mosquitoes. Several vaccine candidates are in development, and to the best of our knowledge, none are fully effective. RTS, S (MosquirixTM), developed by GlaxoSmithKline, was very recently approved by the European Medicines Agency (EMA); however, the vaccine demonstrates only an 18%-36% protection rate, far below the WHO s desired efficacy rate of at least 70%-80%. We have developed a novel malaria vaccine candidate, VLPM01, by using our proprietary vaccine platform based on virus-like-particle (VLP) technology. VLP technology is one of the most powerful methods to develop next-generation vaccines and has solid safety profiles, with several VLP-based vaccines having been successfully commercialized such as those against Hepatitis B virus and human papillomavirus. When presented to the immune system, VLPs evoke effective immune responses without triggering the side effects associated with the native virus. We expect our vaccine platform to produce more powerful immune responses than existing VLP technologies based on preclinical animal studies, and a high protection rate in two malaria-challenged rodent models. Further, based on comparative literature reviews, it is expected that VLPM01 will elicit a far superior response in humans compared to other vaccines under development in addition to the EMA-approved RTS, S vaccine. In this proposal, we request funding support for the next phase of development for VLPM01: (1) the larger scale, standardized manufacturing required by the FDA to produce sufficient amounts of high-grade vaccine material needed for human testing and (2) stability testing of VLPM01, also mandated by the FDA, that is needed
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610330
Entities
People
- Wataru Akahata
Organizations
- United States Army
- VLP Therapeutics (United States)