Malaria, a life-threatening disease caused by parasites and transmitted through mosquito bites, continues to pose a significant global health burden. Nearly half of the world’s population resides in areas susceptible to malaria transmission, spanning 85 countries and territories. In 2022 alone, malaria led to an estimated 249 million clinical cases and 608,000 deaths, with the vast majority occurring in the WHO African Region. The persistent challenge of malaria underscores the need for effective prevention tools, and vaccines represent a promising advancement in this ongoing effort.
Types and Mechanisms of Action
Malaria vaccines primarily target the pre-erythrocytic stage of the parasite’s life cycle, focusing on the sporozoite form injected into the bloodstream by an infected mosquito. These sporozoites travel to the liver, where they mature before infecting red blood cells, leading to the symptomatic phase of the disease. By intervening at this early stage, vaccines aim to prevent the parasite from establishing a full-blown infection.
Both leading vaccine candidates, RTS,S/AS01 and R21/Matrix-M, work by targeting the circumsporozoite protein (CSP), a protein on the surface of sporozoites that aids liver cell invasion. The vaccines trigger the body’s immune system to produce antibodies that block sporozoites from entering liver cells. Additionally, they activate T cells, which target sporozoites that bypass antibody defense.
The RTS,S vaccine contains fragments of CSP linked to a protein from the hepatitis B virus, which assembles into virus-like particles. This structure helps to alert the immune system to CSP, leading to a stronger immune response. R21/Matrix-M is similar, also a virus-like particle-based vaccine utilizing CSP. R21, however, features a redesigned hepatitis B surface antigen fusion, which increases the density of the CSP antigen displayed on the vaccine particle, potentially leading to a greater anti-CSP antibody response.
Current Vaccine Landscape and Efficacy
The current landscape of malaria vaccines features two prominent candidates: RTS,S/AS01, known commercially as Mosquirix, and R21/Matrix-M. The World Health Organization (WHO) prequalified RTS,S/AS01 in July 2022, followed by R21/Matrix-M in October 2023. Prequalification is a prerequisite for procurement by organizations like UNICEF and for Gavi funding.
Clinical trials have demonstrated the efficacy of both vaccines in preventing malaria in children. RTS,S/AS01 showed a protection of 55.8% against uncomplicated malaria in children aged 5 to 17 months in a per-protocol analysis over one year. An 18-month booster provided 36% efficacy against symptomatic malaria and 29% against severe malaria over four years of follow-up. R21/Matrix-M has shown 75% efficacy against clinical malaria over one year in the 5-17 months age group when administered in three doses. A 12-month booster maintained 80% efficacy over one year and 78% against multiple clinical malaria episodes over two years.
Global Implementation and Public Health Impact
Malaria vaccines, initially in pilot programs, are now integrated into routine immunization schedules in African countries. As of December 2024, 17 countries in Africa have introduced malaria vaccines into their routine childhood immunization programs, with 14 of these countries starting their programs in 2024. These countries, bearing approximately 70% of the global malaria burden, have received over 12 million vaccine doses co-funded by Gavi and national governments.
The deployment of these vaccines involves collaborative efforts from global health organizations and governments to navigate logistical considerations. Organizations like WHO, UNICEF, and Gavi are supporting vaccine procurement and delivery, aiming to ensure sufficient supply. The anticipated public health impact includes a reduction in malaria cases, hospitalizations, and deaths in vaccinated populations, contributing to malaria control efforts. For instance, the Malaria Vaccine Implementation Programme (MVIP) in Ghana, Kenya, and Malawi, which delivered RTS,S/AS01 to over 1.7 million children, resulted in a 13% drop in all-cause child deaths.
Safety Profile
Malaria vaccines undergo rigorous testing and continuous monitoring for safety. Common side effects observed in clinical trials and post-market surveillance are generally mild and temporary, similar to other routine vaccines. These typically include pain or swelling at the injection site, fever, headache, and muscle aches. Such reactions indicate the immune system is responding to the vaccine and are normal.
Serious adverse events (SAEs) are rare and thoroughly investigated. In clinical trials, the incidence of vaccine-related SAEs has been low, ranging from 0.0% to 0.3%, with most being fever-related. While earlier studies on RTS,S noted potential signals for meningitis or cerebral malaria, subsequent large-scale programs and analyses have not found these associated with vaccination. Ongoing pharmacovigilance and safety monitoring efforts track any long-term or rare side effects, ensuring the benefits of preventing malaria outweigh potential risks.