Malaria vaccines– latest developments

To the Editor,

Malaria, a mosquito-borne disease caused by the Plasmodium parasite continues to be a serious health issue worldwide. The World Health Organization (WHO) World Malaria Report 2023 reported approximately 249 million cases in 85 malaria-endemic regions, with a total of 608,000 recorded deaths secondary to malaria [1]. From an estimated total of 35.4 million pregnancies, 12.7 million (36%) patients were exposed to malaria during pregnancy [1]. Young children were disproportionately affected with approximately 462,000 (76%) of all malaria deaths reported in children under the age of five [1]. Recent climate change has often been associated with higher rates of malaria transmission [1]. Although the exact relation between the two is complex, frequent extreme weather events such as flooding can lead to malaria epidemics [1].

Significant progress has been made to combat malaria on a larger scale, including new interventions and expanding healthcare access for at-risk populations. The development of malaria vaccines has been an ongoing project since the early 1960s [2]. The parasite’s complex biological system, genomics, life cycle, and ability to evade the human immune system are some instances of barriers to the successful development of a vaccine until recent years [2].

RTS,S/AS01 (Mosquirix™), the first WHO-approved malaria vaccine, was approved in October 2021 for widespread use [3]. Indicated for active immunization, WHO recommends RTS,S to be provided in a schedule of 4 doses starting in infants around 5 months of age, with an additional option of a fifth dose in children residing in high-risk areas [4]. This vaccine was approved after it demonstrated an adequate safety profile in more than 2 million children in Ghana, Kenya, and Malawi in trials ongoing since 2019 [1, 4]. 18 more countries were approved by the WHO, with vaccine rollout scheduled to start in early 2024 [5].

In October 2023, R21/Matrix-M™ became the second WHO-approved malaria vaccine [1, 6]. In December 2023, it was given the prequalification status [5]. Ghana, Nigeria, and Burkina Faso have approved the use of R21/Matrix-M™ in an expanded age range of 5 to 36 months [2]. In January 2024, Phase 3 trial results demonstrated an average of 78% vaccine efficacy over the first year of follow-up in over 4800 young children in Burkina Faso, Kenya, Mali, and Tanzania [7]. Further deployment is expected to start in mid-2024 [3].

Both vaccines, intended for active immunization, are circumsporozoite protein (CSP) vaccines that target the pre-erythrocytic stage [8]. RTS,S was created using genes from the repeating (“R”) and T-cell epitope (“T”) of the CSP of the Plasmodium falciparum parasite, along with a surface antigen (“S”) of the Hepatitis B virus [9, 10]. It also includes an additional Hepatitis B surface antigen (HBsAg) (the extra “S”) [9, 10]. Similarly, R21/Matrix-M™ includes HBsAg fused to the C-terminus and central repeats of CSP, but it lacks the additional HBsAg that is found in RTS,S [11]. AS01 and Matrix-M™ represent the adjuvant systems that enhance and improve the immunogenicity of both vaccines [8]. Known adverse effects are mild to moderate including fever, injection site pain and swelling, and rarely, self-limited febrile seizures [12, 13]. Contraindications for both vaccines include hypersensitivity to either a previous dose or to a component of the vaccines [13].

In conclusion, vaccines have historically proven to be extremely efficient in eradicating diseases such as polio, measles, tetanus, and other diseases. The Coronavirus disease 2019 (COVID-19) pandemic was another example where swift vaccine development helped to reduce mortality and morbidity rates worldwide. In my opinion, these vaccines will help in reducing the malaria burden in at-risk regions to a great extent. However, to eradicate malaria, it is essential to enhance public knowledge and awareness about its transmission, interventions, vector-eradicating techniques, and methods of prevention. I believe that as physicians it is important to be cognizant of the recent advances in immunization efforts against malaria.