Although progress has been made in the last 10 years toward developing malaria vaccines, there is currently no licensed malaria vaccine on the market.
Barriers to Developing a Malaria Vaccine
The development of a malaria vaccine has faced several obstacles: the lack of a traditional market, few developers, and the technical complexity of developing any vaccine against a parasite.
Malaria parasites have a complex life cycle, and there is poor understanding of the complex immune response to malaria infection. Malaria parasites are also genetically complex, producing thousands of potential antigens. Unlike the diseases for which we currently have effective vaccines, exposure to malaria parasites does not confer lifelong protection. Acquired immunity only partially protects against future disease, and malaria infection can persist for months without symptoms of disease.
More than a dozen vaccine candidates are now in clinical development, and one, GlaxoSmithKline Biologicals’ RTS,S, has completed Phase III clinical testing—the first malaria vaccine candidate to advance this far.
Children ages 6–12 weeks and 5–17 months were enrolled in the trial at 11 sites in seven African countries. CDC, in collaboration with the Kenya Medical Research Institute, led the trial at one site in western Kenya.
The trial’s final results, made available in 2015, are a promising advance in development of a malaria vaccine for African children. The RTS,S vaccine reduced clinical and severe cases of malaria by about one-third in 5–17-month-old children over four years who received the three-dose vaccine series plus a booster dose. The vaccine was less effective in children the young infant group. The vaccine was generally found to be safe, but there were a few safety signals that warranted further study, including febrile convulsions, meningitis, and cerebral malaria.
Notably, the vaccine provided this protection in settings where there is ongoing use of other effective malaria prevention and treatment interventions: bed nets, antimalarial drugs, indoor residual insecticide spraying to prevent mosquito-borne transmission, and drugs to protect pregnant women and their newborns from malaria’s adverse effects.
In July 2015, the European Medicines Agency (EMA) gave a positive regulatory assessment of the RTS,S/AS01 vaccine for 5–17-month-olds, but WHO recommended in October 2015 that the vaccine be further evaluated in large-scale pilot studies before recommending it. Large-scale pilots of the vaccine will begin in Ghana, Kenya, and Malawi in 2018 and will include several hundreds of thousands of infants. Pilot evaluations will assess the feasibility of delivering the three-dose vaccine series plus booster through routine health systems, carefully examine the relationship of the vaccine to specific adverse events (febrile seizures, meningitis, cerebral malaria), and also evaluate its impact on all-cause mortality. CDC, in collaboration with KEMRI and several other organizations, will lead the evaluation of the large-scale RTS,S/AS01 pilot in western Kenya.
Alternative dosing schedules for higher efficacy of the RTS,S/AS01 vaccine, including a fractionated third dose, are also being evaluated in separate studies. CDC is leading one of these studies, in collaboration with KEMRI, in infants in western Kenya.
Whole Sporozoite (PfSPZ) Vaccines
Another promising malaria vaccine candidate includes whole sporozoites, the sexual form of the parasite extracted from mosquito salivary glands, which have either been made non-infectious through irradiation or are administered along with chemoprophylaxis. Recent trials have shown that the irradiated whole sporozoite PfSPZ Vaccine made by Sanaria® is safe and well tolerated and had promising protection against malaria when administered intravenously. A collaborative CDC and KEMRI trial in western Kenya has shown that the PfSPZ Vaccine is safe and well tolerated in infants and young children. The ongoing study will have information on the efficacy of the vaccine in infants in spring 2018. Other studies are currently evaluating the efficacy of the PfSPZ Vaccine in different populations in Mali, Gabon, Tanzania, and Equatorial Guinea.
Malaria Vaccines: The Way Forward
The RTS,S/AS01 vaccine and the PfSPZ vaccine products are two of the most promising malaria vaccine candidates to date. Other malaria vaccine candidates are in development or trial phases, including transmission-blocking vaccines that target the sexual stage of parasite development in the mosquito, The world’s leading global health organizations have developed the Malaria Vaccine Technology Roadmap for accelerating development of a highly effective malaria vaccine.
The roadmap includes the following strategic goals for malaria vaccines by 2030:
- Develop and license malaria vaccines with protective efficacy of at least 75% against clinical malaria for areas with ongoing malaria transmission.
- Develop malaria vaccines that reduce transmission and human malaria infection, enabling elimination in multiple settings through mass vaccination campaigns.