PATH’s Center for Vaccine Innovation and Access

Malaria

Accelerating the development of malaria vaccines

Photo: PATH/Gabe Bienczycki

Photo: PATH/Gabe Bienczycki

Even with substantial progress in controlling malaria over the past 15 years, the parasitic disease continues to cause suffering globally, and remains a leading killer of children younger than five in sub-Saharan Africa.

Transmitted through the bites of infected, female Anopheles mosquitoes, malaria causes more than 400,000 deaths annually. While close to one-half of the global population is at risk, sub-Saharan Africa shoulders a disproportionately high disease burden.

Among malaria species, Plasmodium falciparum and Plasmodium vivax pose the greatest threat; however, P. falciparum—predominant in sub-Saharan Africa—is responsible for the vast majority of malaria deaths. By World Health Organization (WHO) estimates, the region accounts for roughly 88 percent of the more than 200 million malaria cases annually and 90 percent of the deaths.

Use of long-lasting insecticidal nets, indoor spraying with insecticides, and effective antimalarial drugs has made this disease increasingly preventable and treatable. WHO also recommends early testing of suspected cases and use of artemisinin-based combination therapies for uncomplicated P. falciparum malaria. Despite progress, however, parasite resistance to drugs and mosquito resistance to insecticides—as well as evidence of changes in biting behavior on the part of mosquitoes—has strengthened the argument for a broader toolkit of malaria interventions.

The potential role for malaria vaccines

In light of the international community’s goals for controlling, eliminating, and eventually eradicating malaria, a vaccine is seen as adding an important and complementary tool to the effort. Investment in malaria vaccine development increased significantly in the first decade of this century and has accelerated development efforts over the past 15 years.

First-generation vaccine

The malaria vaccine community has provided guidance for developing a first malaria vaccine. The Malaria Vaccine Technology Roadmap (PDF 1.92 MB) envisions a first-generation vaccine that has protective efficacy of more than 50 percent against severe disease and death, with protection lasting longer than one year. Given the modest efficacy expected, a first vaccine is meant to complement routine methods that countries use to control malaria.

Within PATH’s Center for Vaccine Innovation and Access (CVIA), GlaxoSmithKline’s (GSK’s) RTS,S vaccine candidate aims to address the need for a first-generation vaccine. Phase 3 trial data demonstrated that three doses of RTS,S reduced malaria cases by almost half in children 5-17 months old over 18 months. Over four years of follow-up, four doses of RTS,S reduced malaria cases in this age group by 39 percent.

RTS,S received a positive scientific opinion from European regulators in 2015. The opinion was followed by a position paper, in which the WHO recommended further evaluation of RTS,S in a pilot implementation program in three to five locations in sub-Saharan Africa. Efforts are now underway to secure funding for the pilots, which will be coordinated by WHO and undertaken in collaboration with PATH, GSK, and other partners.

Next-generation vaccines

PATH is also focusing on the longer-term goal of progressive malaria elimination and eventual eradication. As such, our work targets the development of highly efficacious vaccines that go beyond preventing illness to preventing infection and transmission of the malaria parasite.

The focus is on the following: 1) anti-infection vaccines that seek to build on RTS,S and prevent infection in people bitten by infected mosquitoes, and 2) transmission-blocking vaccines that prevent mosquitoes from becoming infected with malaria parasites when they feed on infected people.

Additional resources