The state of global malaria vaccine development

More candidates are moving through development

Progress toward developing malaria vaccines has accelerated in the last decade. Increased funding, greater awareness, and advances in science and in vaccine technologies have reinvigorated a field that had been constrained by the absence of a traditional market, few developers, and the technical complexity of developing any vaccine against a parasite.

Where we are

Today, the malaria vaccine development field is a dynamic arena of scientific endeavor. Increased funding and research is driving the discovery of new antigens and vaccine technologies, and many more malaria vaccine candidates are moving through the development pipeline.

A 2007 report by the Australia-based George Institute for International Health shows that the global malaria vaccine portfolio has grown from no malaria vaccines in clinical trials in 1985 to 16 candidates in clinical development in 2006 (See figure 1. for current status). In addition, GlaxoSmithKline Biologicals’ RTS,S is poised to enter advanced clinical development—making it the first malaria vaccine candidate to advance this far. The current development plan for RTS,S indicates that the candidate could be submitted to regulatory authorities by 2011.

Challenges to developing malaria vaccines

Even with the recent progress, accelerating development of malaria vaccines remains as complex as ever. Developers face myriad challenges, including:

  • There are no known correlates of immunity for malaria vaccines; therefore, vaccine candidates can only be shown to work (or not work) by going through clinical trials. The need for an empirical process makes developing malaria vaccines expensive and time consuming.
  • Owing to the above, the field would benefit from the availability of diverse target antigens and antigen delivery platforms capable of inducing a variety of immune responses. Few new antigens have been added to the malaria vaccine candidate arsenal over the past decade, and immune-enhancing adjuvants, which are few in number and largely controlled by for-profit entities, are not freely available.
  • The field needs additional, and more rigorously qualified, assays and models for assessing vaccine candidates to inform decision-making along the development pathway.
  • Various business models are needed for ensuring the availability of vaccines once developed.
  • Activities to ensure vaccine financing and use are crucial if a viable candidate is to advance through development and reach those in need.

A blueprint for developing malaria vaccines

The global malaria vaccine community has laid out a blueprint for moving forward, a pathway for developing—by 2025—a malaria vaccine with protective efficacy of more than 80 percent against clinical disease and with protection lasting for many years without a booster immunization. As laid out in the Malaria Vaccine Technology Roadmap, an interim goal is to develop and license a first-generation vaccine by 2015 that has 50 percent protective efficacy against severe disease and death, with protection lasting at least one year without the need for boosting. Evidence suggests that the malaria vaccine community is on track, with RTS,S, to meet the 2015 mark.

Toward the 2025 goal

It is anticipated that, to achieve the level and duration of protection required to achieve the 2025 goal, a vaccine that is more potent and efficacious than RTS,S is likely required.

Successes to date in malaria vaccine development have been observed with candidate vaccines and strategies that target the pre-erythrocytic stage of malaria development—when the parasite, inoculated by the mosquito, takes up residence in a person’s liver prior to being released into the blood. Several novel approaches directed at this stage of the parasite’s life-cycle are in late preclinical development and will enter clinical trials over the next year, or are already in preliminary human clinical trials. One approach, using a weakened form of the parasite inoculated by the mosquito (the sporozoite), enters clinical trials in 2008, while another approach using a cold virus to carry pre-erythrocytic antigens is already in Phase 1 trials.

Blood-stage antigens will continue to be researched and developed based on assessment of the preclinical immune responses induced in small animals. These antigens may be important for augmenting protection provided by pre-erythrocytic vaccines as well as potentially serving as vaccines in their own right if sufficiently potent immunity is induced. Multistage vaccines may well be required to achieve the high level of efficacy called for in the 2025 Technology Roadmap goal.

References

  • Moran M, Guzman J, Ropars A, et al. The Malaria Product Pipeline: Planning for the Future. London, UK: The George Institute for International Health; 2007.
  • Program for Appropriate Technology in Health (PATH), Accelerating Progress Toward Malaria Vaccines. Bethesda, MD: PATH; 2007.
  • Malkin E, Dubovsky F, Moree M. Progress Towards the Development of Malaria Vaccines. Trends in Parasitology. 2006;22(7):292–295.