Suchergebnisse

Vaccines can be extremely cost-effective public health measures. Unfortunately the research and development (R&D) of novel vaccines is suffering from rising costs and declining success rates. Because many vaccines target low- and middle income markets (LMIC), output needs to be maintained at a constrained budget. In addition, scientific neglect and political uncertainty around reimbursement decisions make it an unattractive arena for private investors. The vaccine development pipeline for LMIC thus is in need for a different, sustainable, and cost-effective development model. In conventional vaccine development, objectives for every clinical development phase have been predefined. However, given the scarcity of resources, the most efficient clinical development path should identify vaccine candidates with the highest potential impact as soon as possible. We argue for a custom-made question-based development path based on the scientific questions, success probabilities and investments required. One question can be addressed by several studies and one study can provide partial answers to multiple questions. An example of a question-based approach is the implementation of a controlled human malaria infection model (CHMI). Malaria vaccine R&D faces major scientific challenges and has limited resources. Therefore, early preliminary efficacy data needs to be obtained in order to reallocate resources as efficiently as possible and reduce clinical development costs. To meet this demand, novel malaria vaccines are tested for efficacy in so-called CHMI trials in which small groups of healthy volunteers are vaccinated and subsequently infected with malaria. Early evaluation studies of critical questions, such as CHMI, are highly rewarding, since they prevent expenditures on projects that are unlikely to succeed. Each set of estimated probabilities and costs (combined with market value) will have its own optimal priority sequence of questions to address. Algorithms can be designed to determine the optimal order in ...

BACKGROUND: Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility. METHODS: We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program. RESULTS: We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates. CONCLUSIONS: Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.