Malaria is a disease caused by parasites, primarily transmitted through the bite of infected Anopheles mosquitoes. For centuries, this illness has profoundly impacted human health, contributing to millions of deaths and significantly hindering development in affected regions worldwide. Recognizing the immense burden of this disease, the long-standing need for an effective vaccine has driven extensive scientific inquiry.
The Long Road to a Vaccine
Developing a vaccine for malaria has presented significant challenges, distinguishing it from vaccines for bacterial or viral infections. Unlike simpler pathogens, the Plasmodium parasite, responsible for malaria, possesses a highly complex life cycle involving both human and mosquito hosts. This intricate life cycle means the parasite presents thousands of different proteins, or antigens, to the human immune system as it transforms through various stages within the body.
The parasite’s ability to evade detection and clearance by the human immune system further complicates vaccine development. Plasmodium species have evolved sophisticated strategies to hide within human cells, such as liver cells and red blood cells, minimizing their exposure to immune responses. They can also rapidly change their surface proteins, a process known as antigenic variation, which allows them to continuously escape immune recognition. These biological complexities have meant that early research efforts faced significant hurdles, making the journey toward an effective malaria vaccine challenging.
The First Approved Malaria Vaccine
A historic milestone in the fight against malaria was reached with the development and recommendation of RTS,S/AS01, known by its brand name Mosquirix. This vaccine targets the Plasmodium falciparum parasite, the most lethal malaria species and the most prevalent in Africa. Scientists at GlaxoSmithKline (GSK) initiated its development in 1987, collaborating with the Walter Reed Army Institute of Research. The RTS,S vaccine was further developed through a public-private partnership between GSK and PATH’s Malaria Vaccine Initiative, with support from the Bill & Melinda Gates Foundation.
Extensive clinical trials demonstrated its efficacy and safety. The vaccine works by triggering the immune system to defend against the parasite’s initial stage when it enters the bloodstream and infects liver cells after a mosquito bite. Based on the results from pilot programs in Ghana, Kenya, and Malawi, the World Health Organization (WHO) recommended the widespread use of RTS,S/Mosquirix for children in sub-Saharan Africa and other regions with moderate to high P. falciparum malaria transmission on October 6, 2021. While not providing complete protection, this recommendation marked the first time a malaria vaccine was endorsed for broad use, representing a significant step forward in malaria control.
Expanding the Vaccine Arsenal
Beyond RTS,S, ongoing research continues to expand the arsenal against malaria. A second vaccine, R21/Matrix-M, has recently gained prominence. Developed by the Jenner Institute at Oxford University and manufactured by the Serum Institute of India, R21/Matrix-M was recommended by the WHO in October 2023. This vaccine also targets the Plasmodium falciparum parasite and showing high efficacy in clinical trials.
R21/Matrix-M has shown particular promise, demonstrating 75% efficacy against symptomatic malaria cases in highly seasonal transmission areas over 12 months after a three-dose series. Its development is further supported by the Serum Institute of India’s capacity to produce 100 million doses annually, with plans to double this capacity, making it a potentially cost-effective and widely deployable solution. The availability of R21/Matrix-M alongside RTS,S is expected to help close the demand-supply gap for malaria vaccines, offering an important additional tool to protect more children in malaria-endemic regions. Research into other promising candidates is also underway, reinforcing the global commitment to continuous progress in malaria prevention.