Summary:

This proposal intends to set-up a coordination of the public-funded malaria vaccine development in Europe in intimate co-ordination with WHO/IVR, in the context of overall global efforts, by establishing a collaborative strategy in malaria vaccine development consisting in formulation of shared strategic plans, and in development of common tools, optimised resources and iterative activities.

This project will stimulate the community of problem-solvers by sharing information, by establishing a correct balance between collaboration and competition, by identifying and prioritising the most critical scientific, technical and regulatory questions. This will constitute a pool of resources which can rapidly be directed to obtain answers to these questions. This project will be the basis for the implementation of common standards for assessing research results and to maximise the sharing and the use of data, resources and knowhow. The strategy for malaria vaccine development is based on two pillars: pharmaceutical development and clinical development.

The overall objective of the proposal is to prepare for the creation of the enabling environment in the field of malaria vaccine development by consolidating the Network of complementary expertise and resources. This SSA will focus on:

1. Developing and implementing a rationale screening for malaria vaccine antigens, addressing the scientific, technical, regulatory and ethical constraints. This implies to develop reliable assays for in-vitro and animal pre-clinical studies
2. Design of clinical development strategy for malaria vaccine candidates developed in Europe

• Definition of the go/no go criteria for entering in phase Ia clinical studies
• Defining safety evaluation criteria
• Defining immunological evaluation criteria. This implies to develop the methodology for standardisation of safety and immunological criteria, addressing the scientific, technical, regulatory and ethical constraints.

Background:

Malaria vaccine development will require a series of co-ordinated steps from basic research and identification of lead vaccine candidates, GMP manufacture of these lead candidates, to their evaluation for safety and immunogenicity (Phase I and when appropriate Phase II trials) in Europe, before they can be clinically tested in Africa for safety, immunogenicity and efficacy (Phase I, II and III trials). Before licensure, these vaccines will be tested in large multi-centre trials on large numbers of individuals (tens of thousands) as required by national and EU Regulatory authorities.

There has been considerable investment at the national and EU level in malaria basic research, but this has not been matched by investment in moving experimental vaccines through manufacturing and clinical testing. Common guidelines on harmonised preclinical and clinical evaluation and agreed decision-making criteria are needed to provide a more rational basis for the development of malaria vaccines.

Aim:

The malaria vaccine community should be supported by providing a sound basis for the decision process to support the development of more innovative and rationale-based vaccines. EURHAVAC will propose to the malaria vaccine scientists four main action plans:

1. For the definition and the implementation of decision-making process for pharmaceutical development
2. For the definition and the implementation of a clinical development strategy
3. For the harmonisation of the evaluation criteria of malaria vaccine
4. For the dissemination of the knowledge and the information yielded by the three first action plans

The first specific objective will be to develop algorithms for decision making from the scientist research to the manufacturing of a GMP clinical batch.

The second specific objective is to design strategic clinical development plans for the four major categories of malaria vaccines developed in Europe 1) Preerythrocytic (sporozoite) vaccines, 2) Asexual blood-stage (erythrocytic) vaccines, 3) Transmissionblocking vaccines, 4) Pregnancy Associated malaria vaccines.

The third specific objective is to address assay development, optimisation and standardisation, in intimate collaboration with WHO/IVR and as a contribution to on-going coordination activities.The fourth specific objective is to disseminate the information and the documentation to other groups involved in malaria vaccine development, worldwide, through already existing international cooperations.

Expected results:

This SSA will meet the urgent need to create an enabling environment capable of coordinating resources - available in the European Research Area - into a network proficient in managing the existing and desired knowledge. Such knowledge management will provide for the development of strategice approaches to malaria vaccine development and evidence-based benchmarking.

There are a limited number of SMEs that are involved in malaria vaccine pharmaceutical development, and during the last three years, a major effort has been developed in European Biotechs to achieve the level of quality required by the EC directive on Good Manufacturing Practice. However, the transfer of the candidate vaccine from the research laboratory to the manufacturing field is still suffering of the poor involvement of SMEs at the research laboratory, when production experts should bring to the scientist the methodology for process development and for the quality control assay development. By addressing the decision process and the assay development, EURHAVAC will enable and promote an early concert and collaboration of academic scientist and SMEs and will accelerate the transfer of technology.

Potential applications:

Vaccine development is an iterative process on a continuous flow. The complexity of the current European malaria vaccine research is mainly due to the difficulties to establish strong bridges between the different actors during the development process, as shown in the following figure. EURHAVAC will play a major role reconciling the different actors through the decision-making process and the development strategy.

Coordinator: