A global initiative backed by the World Health Organisation aims to develop and license a malaria vaccine with more than 80% efficacy against clinical disease and a protective span of more than four years by 2025.

The interim goal of the Malaria Vaccine Technology Roadmap is to develop and license a first-generation malaria vaccine, with 50% protective efficacy against severe disease and death lasting longer than one year, by 2015.

The process started more than two years ago, when the WHO’s Malaria Vaccine Advisory Committee called for a collective effort to explore and address the challenges impeding progress towards an effective malaria vaccine. Development of the Roadmap, which was officially launched at the Global Vaccine Research Forum in Bangkok this week, was sponsored by the Bill and Melinda Gates Foundation and the Wellcome Trust. The PATH Malaria Vaccine Initiative co-ordinated the work, involving more than 230 experts from 100 organisations in 35 countries.

Vaccine development efforts will be targeted at Plasmodium falciparum, the most deadly form of the malaria parasite. Despite the use of antimalarial drugs such as Novartis’ Coartem (artemether plus lumefantrine), the disease still kills more than a million people out of 300-500 million cases worldwide each year. As WHO points out, development of a malaria vaccine has been hampered by incomplete understanding of the mechanisms of malaria infection, as well as inadequate resources, limited private-sector involvement and uncertain mechanisms for procuring and distributing an effective product.

There are currently more than 30 malaria vaccine candidates under development, far more than there is capacity or funding – especially in endemic countries – to investigate in clinical trials, WHO notes.

Aligning research efforts

The Roadmap presents a strategic plan for aligning research efforts and for developing and distributing a safe, effective and affordable vaccine to prevent malaria in children under five years old in sub-Saharan Africa and other highly endemic regions. It sets 11 priorities under four headings for pursuing more co-ordinated vaccine development.

In the research field, these include standardising procedures to compare immune responses to vaccine candidates. Vaccine development should encompass multi-antigen, multi-stage and weakened whole-parasite approaches, the Roadmap recommends. Under the rubric of ‘key capacities’ comes building clinical trial capacity to good clinical practice standards in malaria-endemic regions. Among the priorities for policy and commercialisation are developing novel regulatory strategies to expedite vaccine approvals.

The Roadmap is framed as a public health initiative and makes only occasional mention of pharmaceutical industry involvement. Indeed, it comments that expertise in formulation and process development are concentrated mainly in pharmaceutical companies “where, with few exceptions, there is limited investment in malaria vaccine development."

The recent resurgence of interest in vaccines that, spurred on by the spread of HIV/AIDS and the threat of an avian influenza pandemic, has seen big pharma players such as Novartis (through its acquisition of Chiron) and GlaxoSmithKline invest heavily in the sector has not generally been replicated for diseases specific to the developing world.

Pharma involvement

Nonetheless, a number of companies, ranging from major players such as the GSK to niche operators like the Dutch Crucell, the German Apovia and the UK’s Adprotech, are working on malaria vaccines. Clinical trial results so far for GSK’s investigational vaccine Mosquirix have been highly promising, with a strong safety profile and potential to reduce the overall incidence of severe disease by 58%, or by 77% in children under two years old.

Mosquirix, which is being backed by the PATH Malaria Vaccine Initiative with funding from the Bill and Melinda Gates Foundation, is expected to enter Phase III trials next year. It could be 2010 before the vaccine – already nearly 20 years in the making – actually reaches the market, though.

In fact, closer scrutiny of the participants in the Malaria Vaccine Technology Roadmap process does reveal the involvement of pharmaceutical companies including GlaxoSmithKline, GeneMedix, Sanofi-Pasteur, Eli Lilly and Merck & Co.

Moreover, the Roadmap itself makes some tentative gestures towards public-private partnership. Addressing the challenge of finding capacity to manufacture and formulate the wide range of vaccine concepts under development, it proposes establishing an accessible process development centre or a set of collaborating research organisations operating as a ‘virtual center’. Either approach “would most likely represent a partnership among academic, commercial or contract, and government institutions," the document comments.

Tackling the issues of commercialisation, the Roadmap highlights the need for “a viable pricing model that incorporates the unique costs and benefits of commercialising vaccines that exclusively target diseases of the poor." Pharmaceutical companies currently engaged in vaccine development can help to identify suitable factors for inclusion in such a model (e.g., tiered pricing), it suggests, adding that a successful model could “encourage industry participation without compromising corporate fiscal health." By Peter Mansell