Does the recent approval of the RTS, S vaccine mean the end of malaria?
In recent weeks, the world was struck with very exciting news related to the fight against malaria. While a vaccine against malaria called RTS, S/AS01 (RTS, S), with market name Mosquirix, received a positive opinion from European Medicines Agency (EMA) already in 2015 [1], in October of this year it became the first-ever vaccine against malaria with WHO’s recommendation for widespread use in African regions with moderate to high P. falciparum malaria transmission [2]. It is indeed a historic event and it was hailed as such in the media [3-5]. Some news providers even went as far as claiming that it can save the lives of hundreds of thousands of children annually [6-8]. Unfortunately, these claims are not entirely precise.
Despite decades of global efforts to eradicate it, malaria still remains a major burden. Just in 2019, there were around 229 million cases of malaria worldwide, of which 409’000 resulted in death. Furthermore, 67% of the victims were children below 5 years of age [9]. The struggle to contain this disease is complicated due to its aetiology.
Malaria is caused by parasites from the genus Plasmodium [10]. Among them, the most widespread species is also the one responsible for the most severe symptoms i.e., P. falciparum. Unfortunately, the fight against malaria is taking so long because of the complexity of these parasites, their interactions with hosts, and their lifecycle [11]. Throughout their lifecycle, they reside within two host organisms i.e., they start by infecting mosquitoes, which then transmit the parasite to humans by biting them. While in these two hosts, malaria parasites greatly change the structure, increase in number, and change the organs in which they reside. In humans, they start their journey in the skin. Next, they travel to the liver to then move to the blood and infect red blood cells. At this stage, the parasite undergoes its most rapid replication, leading to massive rupture of the host’s red blood cells. This stage is responsible for the symptoms of the disease [12, 13].
Unfortunately, not only the complexity of the parasite but also the abundance of mosquitoes being vectors infecting people make this issue still unresolved. Until now, the main focus of measures against malaria was put in the prevention of mosquito bites using tools such as sprays against insects, window- and bed-nets, etc. When these preventative measures failed, patients had to be treated once they already developed the disease [9]. That is why an efficient vaccination against malaria-causing parasites is desperately needed. The newly approved RTS, S vaccine contains a portion of a pathogen-derived protein called circumsporozoite protein (CS). It is present on the parasite’s surface during the lifecycle stages preceding infection of the liver [1]. Thus, this vaccine should prepare the host’s immune response for the elimination of the parasite before it reaches multiplication stages and induces symptoms of the disease.
The RTS, S vaccine had been in development already since 1987 until it finally managed to reach testing in Phase 3 clinical studies in 2009 (more about clinical trials in this article). These studies were performed in 7 sub-Saharan African countries with 15’459 participants [14]. They were conducted to test the efficacy and safety of the vaccine after injection of 3 and 4 doses. The vaccine showed to be safe except for an increased risk of febrile seizures. However, the effect was short-lasting and the affected patients recovered in up to 7 days. Furthermore, the efficacy after 3 doses reached 28.3%, while after 4 doses – 36.3%. Unfortunately, these results were decreasing over time [15].
In conclusion, RTS, S has the potential to help many people in dire need of effective measures to fight malaria. Unfortunately, it is not a solution that will lead to the eradication of malaria as yet. Even when the data from Phase 3 trials were further examined, it was shown that while the average efficacy of the RTS, S vaccine was 36.3%, it goes up to 60% for participants coming from households with access to proper sanitary and preventative resources [16]. Hence, this vaccine is a step in the right direction, but the fight against malaria is arduous and far from over.
References:
- EMA, Mosquirix: Product Information, E.M. Agency, Editor. 2020: ema.europa.eu.
- WHO, WHO recommends groundbreaking malaria vaccine for children at risk, W.H. Organization, Editor. 2021, World Health Organization: who.int.
- Maxmen, A., Scientists hail historic malaria vaccine approval – but point to challenges ahead. Nature, 2021.
- Mandavilli, A., A ‘Historic Event’: First Malaria Vaccine Approved by W.H.O., in The New York Times. 2021: nytimes.com.
- Okumu, F., Historic yet imperfect: Malaria vaccine brings hope but the fight is far from over, in STAT. 2021: statnews.com.
- Kosarzycki, R., Jest pierwsza szczepionka na malarię. Może uratować ćwierć miliona dzieci rocznie, in Spider’s Web. 2021: spidersweb.pl.
- Preidt, R., WHO Approves First Malaria Vaccine, a Lifesaver for Children Worldwide, in U.S. News. 2021: usnews.com.
- Obiezu, T., New Malaria Vaccine to Benefit Hundreds of Thousands of African Children, in VOA. 2021: voanews.com.
- WHO, World malaria report 2020: 20 years of global progress and challenges., in World Malaria Report, G.W.H. Organization, Editor. 2020, World Health Organization: WHO.
- Norman, F.F., et al., Parasitic infections in travelers and immigrants: part I protozoa. Future Microbiol, 2015. 10(1): p. 69-86.
- Renia, L., et al., Vaccination against malaria with live parasites. Expert Rev Vaccines, 2006. 5(4): p. 473-81.
- Acharya, P., et al., Host-Parasite Interactions in Human Malaria: Clinical Implications of Basic Research. Front Microbiol, 2017. 8: p. 889.
- Cowman, A.F., et al., Malaria: Biology and Disease. Cell, 2016. 167(3): p. 610-624.
- Laurens, M.B., RTS,S/AS01 vaccine (Mosquirix): an overview. Hum Vaccin Immunother, 2020. 16(3): p. 480-489.
- RTS, S.C.T.P., Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet, 2015. 386(9988): p. 31-45.
- Gyaase, S., et al., Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status. BMC Public Health, 2021. 21(1): p. 240.