"We have money to buy bed nets, we have money to buy mosquito sprays, and yet, my son had malaria. What about the little boy who lives in a village, probably has no bed nets, and will probably take about 24 hours before getting to the nearest health facility? What happens to that child? We need to prevent the child from getting malaria in the first place." - malaria champion, Malaria Vaccine Advocacy Fellowship

Vaccine Development

At the beginning of this year, the Bill & Melinda Gates Foundation pledged $10 billion over the next ten years towards research, development and delivery of vaccines to the world's poorest countries and called for this period to be the "Decade of Vaccines". However, malaria vaccine development has traveled a long, uneven road. The combination of extremely limited funding, extremely difficult science, and relative lack of interest in the industrialized world has made it difficult to progress as quickly as malaria's toll demands. Overcoming the unique challenges of malaria vaccine development requires innovative partnerships and financing strategies.

Diverse Approaches to developing malaria vaccines attempt to break the cycle of malaria infection at different stages of the parasite (Plasmodium falciparum)'s development.

1. Malaria infection begins with a mosquito bite that injects the parasite, in the form of sporozoites, into a person's bloodstream
2. Within minutes, the sporozoites penetrate the liver cells
3. Over the next 2 weeks, sporozoites in the liver cells develop into merozoites. The infected person has no signs or symptoms
4. Merozoites burst out of the liver cells and enter the bloodstream
5. The merozoites invade red blood cells, multiply, and rupture out of these cells every two days.
6. The infected person develops fever, chills, and other symptoms
7. After ten days, infected red blood cells release male and female gametocytes (sexual forms) that have matured from some of the merozoites within the red blood cells
8. As a mosquito feeds on an infected person, gametocytes move into the mosquito, where they mature into sporozoites, travel into the salivary glands, and the cycle repeats.

Pre-erythrocytic vaccines target sporozoites, blood-stage vaccines target merozoites, and transmission-blocking vaccines target gametocytes. Research into pre-erythrocytic vaccination, possibly in combination with blood-stage targeting, has proven the most effective. A vaccine would close the gap left by other preventative and treatment interventions such as bed nets, indoor residual spraying, ACTs and intermittent treatment for pregnant women.

The PATH Malaria Vaccine Initiative (MVI) is a global program committed to accelerating the development process of a malaria vaccine for children under 5 and pregnant women in Sub-Saharan Africa. MVI was established in 1999 as a PATH program through a grant from the Gates Foundation and works not only to identify promising vaccine candidates and systematically move them through the development process, but also to ensure that the countries most in need of these vaccines will have access and be ready to implement as soon as one becomes available. MVI is currently conducting late-stage clinical testing of a malaria vaccine through its leading candidate GlaxoSmithKline Biologicals' RTS,S in 11 sites in seven African countries - Gabon, Mozambique, Tanzania, Ghana, Kenya, Malawi, and Burkina Faso. Clinical development of vaccines is typically carried out in four stages.

• The first two phases focus on finding a safe dosage, observing how the product affects the human body, measuring immonogenicity and efficacy against the disease, and monitoring safety and initial side effects. 
• Phase 3 assesses the safety and efficacy of the vaccine in tens of thousands of volunteers in a large enough sample to ensure its success under varied conditions. 
• If phase 3 trials demonstrate safety and sufficient efficacy, the next steps would be licensure and the final Phase 4, which involves long-term, post-licensure safety to address the possibility of rare or long-term side effects. 

The Phase 3 trial for GSK Bio's malaria vaccine was launched in May of 2009 by MVI and GSK Bio, along with leading African research institutions, and will involve up to 16,000 infants and young children who would most benefit from an effective malaria vaccine.

The Malaria Vaccine Advocacy Fellowship through MVI helps to bridge the worlds of science and policymaking by training "policy champions" who will advocate to help ensure that when it becomes available, a vaccine will reach the people who need it the most. This initiative is working to close the financial gap between the availability of life-saving interventions and developing countries' access to them, as well as the communication gap between scientific discoveries and policy realities, which could mean the difference between life and death for millions of children in Africa.