PATH malaria vaccine initiative (MVI): Perspectives on the status of malaria vaccine development

Abstract

In 2006, the malaria vaccine community communicated a goal to develop and license a highly effective P. falciparum malaria vaccine by 2025, with a landmark goal of licensure of a P. falciparum vaccine that could afford partial protection from severe malaria and death by 2015.1 Significant progress has been made toward the landmark goal, with RTS,S/AS02 reporting 57.7% reduction in severe malaria cases in a Phase 2b study,3 and the community awaiting the impact on severe malaria of an improved formulation, RTS,S/AS01, that has demonstrated 53% protection from clinical disease in Kenyan and Tanzanian children.2 Initiation of a Phase 3 study involving up to 16,000 African children, across 11 clinical sites, was initiated in May 2009, suggesting that the 2015 landmark goal is in sight. Intense efforts are underway toward reaching the 2025 goal to develop and license a vaccine with > 80% effectiveness for more than 4 years, although significant progress remains to be made. A strategy that builds on the success of RTS,S may be most likely to succeed, with heterologous prime-boost studies using adenovirus-expressing CSP a leading contender in the near term.15 In addition to approaches that maximize the potential of B and T cell responses primed by CSP, many of the existing pre-erythrocytic and blood stage antigens remain to be fully investigated for their vaccine potential, with alternate delivery vehicles or antigen combinations offering particular promise. New target antigens are expected to emerge through discovery efforts exploiting genomic and proteomic data, protective efficacy data from whole parasite vaccine approaches, and an increased understanding of the biology of P.falciparum merozoite invasion. Further, the advancement of purified, irradiated-sporozoites to initial efficacy studies represents an important milestone in attempts to build on the most effective malaria vaccine tested to date and hold significant promise. The scope and expectation for malaria vaccine development has expanded dramatically in recent years, in large part due to the renewed focus on control, elimination and eventual eradication efforts. As a result, there is an increased effort in developing vaccines that could protect from clinical malaria caused by P. vivax, as well as vaccines that can break the cycle of transmission for all Plasmodium species that infect humans. Novel P. vivax and TBV vaccines will commence initial clinical testing over the next few years; these efforts will need to be accompanied by increased efforts focused on developing appropriate preclinical and clinical assays and model systems to most effectively support development of these vaccines. In the case of TBVs, novel regulatory mechanisms will be needed to be identified through collaboration with regulatory authorities to ensure that they keep pace with product development. The financial resources currently applied to malaria vaccine development are insufficient given the magnitude of the task at hand: to develop more effective P. falciparum vaccines, P. vivax vaccines, and transmission blocking vaccines that could be used in elimination and eradication efforts. In 2007, the Australia-based George Institute for International Health showed that global spending on malaria vaccine R&D represented just 3.5 percent of the world's total R&D investments in neglected diseases, in turn a small fraction of investments in health R&D overall.73 In addition to securing additional resources to maximize potential for success, funders, through organizations such as The Malaria Vaccine Funders Group (MalVFG), could maximize the impact of available resources by coordinating closely development efforts. © 2010 Landes Bioscience.