Comparative decline in funding of European Commission malaria vaccine projects: what next for the European scientists working in this field?

Since 2000, under the Fifth and subsequent Framework Programmes, the European Commission has funded research to spur the development of a malaria vaccine. This funding has contributed to the promotion of an integrated infrastructure consisting of European basic, applied and clinical scientists in academia and small and medium enterprises, together with partners in Africa. Research has added basic understanding of what is required of a malaria vaccine, allowing selected candidates to be prioritized and some to be moved forward into clinical trials. To end the health burden of malaria, and its economic and social impact on development, the international community has now essentially committed itself to the eventual eradication of malaria. Given the current tentative advances towards elimination or eradication of malaria in many endemic areas, malaria vaccines constitute an additional and almost certainly essential component of any strategic plan to interrupt transmission of malaria. However, funding for malaria vaccines has been substantially reduced in the Seventh Framework Programme compared with earlier Framework Programmes, and without further support the gains made by earlier European investment will be lost.


Background
Approximately one million people die each year from malaria, mostly African children under the age of five and pregnant women [1,2]. Malaria is, therefore, one of the major global killer diseases and one of the world's biggest public health problems [1,3]. As malaria is mainly prevalent in low-income countries, it places a disproportionately heavy economic burden on endemic countries, contributing to poverty and limiting economic development [1,4].
Malaria is a complex disease, which is transmitted to humans through the bite of the female Anopheles mosquito inoculating protozoan parasites of the genus Plasmodium. There are five types of human malaria, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi, with P. falciparumand P. vivax being the most common and P. falciparum being the most deadly [1,2].
A protective malaria vaccine that prevents or reduces clinical malaria and associated mortality, as well as reducing transmission, will have a major impact on global human health and socioeconomic development. There is considerable optimism that a malaria vaccine can be developed, as immunity developed following natural infection eventually prevents mortality and protects against clinical disease [3].
A malaria vaccine developed by GlaxoSmithKline (GSK) is being tested in various African countries in Phase III clinical trials, following earlier relatively promising results indicating that perhaps 40-50% of immunized children were protected against natural infection for a significant period [5]. However, it seems unlikely that GSK's RTS, S pre-erythrocytic stage vaccine will generate higher levels of protection in Phase III clinical trials than those achieved in Phase II clinical trials and it is doubtful whether the RTS, S vaccine will have any impact on reducing malaria transmission. To achieve elimination and eventual eradication, it is clearly necessary to intensify the research and development effort to obtain more protective, longer lasting malaria vaccines, including vaccines which also protect against other species of malaria, particularly the very widely transmitted P. vivax.

History of European Commission funded malaria vaccine projects
Under the Fifth Framework Programme (FP) plan for Research and Technology Development (1998)(1999)(2000)(2001)(2002), the European Commission (EC) funded a broad range of research activities related to the three major poverty-related diseases (PRDs), HIV/AIDS, malaria and tuberculosis. A total of 24 malaria projects were supported in this period, with a total budget of approximately € 29 million, of which around € 17 million was dedicated to malaria vaccine projects [1,6]. Increased funding for PRD research was provided in FP6 (2002)(2003)(2004)(2005)(2006)) and a portfolio of 17 malaria projects was established, with an overall budget of about € 64 million, of which almost € 20 million was dedicated to malaria vaccine projects [1].
In the current FP7 plan, (2007-2013), efforts were made to capitalize on the advances achieved under FP6 by improved integration of basic malaria research with more robust research and management structures to translate research results into therapeutic drugs or vaccine candidates. By the end of 2010, halfway through the FP7, a total of nearly € 80 million was earmarked for malaria research. However, only around € 10 million was earmarked for malaria vaccine research [1]. This probably reflected optimism that the GSK RTS, S vaccine would translate well into the developing global anti-malaria campaign and fuelled suggestions that improved vaccines were not a priority.
The past and present EC funded malaria vaccine projects under FP5, FP6 and FP7 are listed in Table 1, 2 and 3 respectively [1].

Key successes, their impact and future perspectives
Vaccines are one of the most effective ways to protect people against infectious diseases, and one of the most cost-effective measures of public health. A malaria vaccine is unlikely to be developed if not supported by public sector and charitable funding and international public organizations, such as the EC [7].
Useful and significant advances have already been achieved by several malaria vaccine projects funded by the EC. A number of its malaria vaccine development projects are in the clinical testing process and will report in the next period. Current EC strategies clearly complement those of other international agencies in this area and have the potential to make a major impact on malaria vaccine development projects. It is, therefore, critical that the EC continues to build on the major advances in understanding immunity to malaria that have been achieved and on several successes in raising immunogenicity of candidate vaccines. Rather than abandon this field, mechanisms for continuing to develop more effective malaria vaccines by building on the current RTS, S successes should be established [7].

Conclusions
To maintain and consolidate the European vaccine development infrastructure and exploit the considerable depth of European expertise in this area, continued funding for malaria vaccine research is essential. Doing otherwise will ensure that European vaccine R&D teams, in both