The European Network for Harmonisation of Malaria Vaccine Development
Basic research in the field of malaria parasitology has allowed several research groups to discover numerous malaria antigens that may be considered for formulation as potential vaccine candidates. From this initial stage of vaccine development, a finite set of well defined guidelines are missing which support and guide the development of experimental vaccines towards a safe, efficacious, affordable and widely available malaria vaccine. Consequently, the global portfolio of experimental malaria vaccines is very unbalanced, as shown by the status of the commonly studied MSP1 and CSP antigens. In 2004, among the 90 ongoing malaria vaccine projects, these two antigens represent 40% of the global portfolio, and 56% of the projects in phase I clinical trials. Thus, the limited research funding available for malaria vaccine development is dispersed over several similar projects and handled by different groups without concert or collaboration resulting in a questionable cascade of phase I clinical trials. This problem is further compounded as poor clinical design provides non-comparable results due to the lack of harmonisation on design, methodology and evaluation criteria. This fragmentation is continually increasing, and is currently a major issue for global and European malaria vaccine development. Therefore, we are working in collaboration with the World Health Organisation and the malaria vaccine community to concentrate on formulating decision making processes for supporting the development of more innovative and rationale-based vaccines that are carefully guided through design and production into clinical trials and so are not hampered by inexperience or competition.
The project aimed at establishing the coordination of public-funded malaria vaccine development in Europe, in cooperation with World Health Organization (WHO)/IVR, and involves the formation of a collaborative strategy for malaria vaccine development to define, harmonise and standardise the optimal immunological criteria for:
- Malaria antigen selection
- Selection of appropriate production/expression systems
- Selection of the presentation/adjuvant systems
- Define and harmonise the product specifications in relation to the regulatory requirements of European and International guidelines
- Define and harmonise the production criteria in order to ensure the creation of an affordable vaccine
Additionally, the project addressed the design of a clinical development strategy for malaria vaccine candidates developed in Europe including:
Definition of the go/no go criteria for entering phase 1a clinical studies
Definition of safety evaluation criteria
Definition of immunological evaluation criteria
In tandem, the development of methodologies for standardisation of safety and immunological criteria related to scientific, technical, regulatory and ethical constraints were addressed via three workshops held in collaboration with the European Commission and WHO/IVR.
Sienna 11 - 13 December 2007
Functional Assays in the Development of Asexual Stage Malaria Vaccines
Copenhagen 5 -6 February 2008
Optimising Decisions Making Processes in Malaria Vaccine Design
Brussels 21 - 22 October 2008
Safety Harmonisation in Pre-Licensure Clinical Trials
In collaboration with Dr. Vasee Moorthy, the Chair of the Malaria Vaccine Funders’ Group (MVFG), the Copenhagen and Brussels reports have been filed on the MVFG website. All reports can be freely accessed in their full version. See www.euvaccine.eu/news-events/meeting-reports for the posted reports. In addition the findings of the EURHAVAC project have been presented as part of EVI’s ongoing activities in numerous presentations given by the staff of EVI to external partners and collaborators.
A summary table has been prepared entitled Assessment Criteria for Evaluation of Malaria Vaccine Concepts prior to Clinical Lot Production: Rationale for choice of antigen
The preclinical selection criteria from the Copenhagen Workshop have been applied to the European Malaria Vaccine Development Association (EMVDA) candidate selection process. The selection criteria were applied to the EMVDA external call, which was officially published on 31 March 2008 with the title, "Call for Selecting New Potential Malaria Vaccine Candidates and the Developing Institutions to Enter into EMVDA". The criteria were also applied to an EMVDA internal call which was launched on 27 April 2009 entitled, "Call for selecting malaria vaccine candidates to enter into Good Manufacturing Practice production and phase Ia clinical trials". The criteria are provided as part of the application pack to enter funding, and applicants are requested to consider the criteria when preparing their application. The Copenhagen workshop report on “Malaria vaccines – how and when to proceed” (which also references the criteria) has been published in Trends in Parasitology.
The recommendations from the Brussels workshop have been fed into the project Optimisation of the Development of Poverty Related Diseases Vaccines by a transversal approach, addressing common gaps and challenges (INYVAX) project. This workshop highlighted several highly complex issues, some of which are being addressed within INYVAX. The workshop report has been made available to EVI’s network so that clinical researchers can be made aware of the current issues. In addition, the report has been forwarded to the Brighton Collaboration for consideration.
The recommendations from the Siena workshop have been fed into the proejct Initiative on Optimising Malaria Vaccine Lab Assays Evaluation (OPTIMALVAC). The group consensus was that development of a set of high quality reagents should be the primary area of focus. A pilot study was designed in which the three Growth Inhibition Assay labs (National Institutes of Health, Walter Reed Army Institute of Research, Biomedical Primate Reserch Centre) will test each other’s animal reagents in a coded fashion. The National Institute for Biological Standards and Control (NIBSC) should receive samples from donor labs, code them and send samples back out to participating labs. Each lab was to perform assays using their own Standard Operating Procedures (SOP) on two different occasions. Data were reported back to NIBSC, who analysed and reported back the results in a blinded fashion to the group. It is hoped that this will ultimately provide some indication of how comparable results are from different labs using different SOP as well as providing a measure of internal variability.