In the midst of the COVID-19 pandemic, malaria, another life-threatening disease continued to disproportionately affect Sub-Saharan Africa. In 2020, there were 245 million malaria cases and 625,000 deaths according to the WHO’s World malaria report. There were 247 million cases and 619,00 deaths the following year. The demographic affected the most? Children under 5. They account for nearly 95% of all cases and 80% of deaths. Malaria continues to be one of the leading causes of childhood illness and death in Sub-Saharan Africa.
Malaria is a mosquito-borne infection caused by parasitic Plasmodium species. Malaria cases have been described as early as 2700 BC and have since been documented by numerous ancient civilizations1. Today, malaria is prevalent throughout regions of Africa due to its native mosquito species (Anopheles), its climate, and the lack of resources and infrastructure to combat the disease2. While intervention strategies such as antimalarial drugs and insecticide-treated bed nets have been developed against the disease to mitigate it, one tool crucial to eradicating the disease has been unavailable until recently, a vaccine.
Development of a malaria vaccine has been challenging on multiple fronts.
Scientifically, targeting the plasmodium parasites that cause malaria is difficult3. The parasite takes on multiple forms during its life cycle in humans. During infection, antibodies are produced against each of these forms and immunity from these antibodies are short-lived. Similarly, a vaccine would have to be made against one or more of these forms in order to be effective which complicates research and development efforts.
Economically, the market for malaria is not big enough to warrant investment by most pharmaceutical companies or government entities. Unlike the SARS-CoV-2 virus, malaria is no longer a global problem. It primarily affects Africa, parts of South America and South Asia. Vaccine development is costly, and the complexity of its parasitic target worsens matters. Additionally, malaria vaccines’ most crucial demographic are children under 5. Trials would first have to be conducted in adults and then in children, significantly increasing cost and time required to vet a single vaccine candidate. Funding for neglected diseases such as malaria has also declined in recent years, thanks in part to the COVID-19 pandemic, exacerbating the problem further4.
Socially, there has not been a sense of urgency. Ashley Birkett, Director of the PATH Center for Vaccine Innovation and Access, puts it simply, “they’re not Europeans, they’re not Australians, they are poor African children. Unfortunately, I think we have to accept that that is part of the reason for the lack of urgency in the community”5.
After 35 years of overcoming these challenges and $200 million later6, the world’s first malaria vaccine was approved in October 20215.
RTS,S (also known by its brand name, Mosquirix) is a malaria vaccine that targets the circumsporozoite protein, a surface protein present during the liver-stage of P. falciparum‘s life cycle. It offers a 30% reduction in severe malaria in fully vaccinated children4. Development on RTS,S began in the 1980s and large scale pilot studies are set to be completed this year3. Current data shows that the vaccine is effective regardless if other prevention tools (like bed nets) are in place. While 30% may seem low, especially in an era of COVID vaccines boasting 90%+ efficacy, research estimates that the RTS,S vaccination regimen could prevent millions of malaria infections and thousands of deaths in small children7. Furthermore, its efficacy can be boosted up to 60% when combined with other interventions like antimalarial drugs8.
However, unfair comparisons to the COVID-19 vaccines are not the only objections to this particular malaria vaccine. Many of the factors that hindered its development will also be impacting its rollout. RTS,S costs about $5 per dose8, and the supply will be limited with distribution beginning later this year or in early 20246.
Fortunately, there are even more promising vaccines on the horizon.
In 2021, a new vaccine candidate began to show promise. The PfSPZ vaccine is made with a live-attenuated form of the blood-stage form (sporozoite) of P. falciparum, and there is future work planned to test its efficacy against the another major malaria causing Plasmodium species, P. vivax. Recently, a study led by the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health demonstrated ~46% efficacy post-vaccination9.
Researchers at the University of Oxford had also been developing their own malaria vaccine. R21/Matrix-M, targets the same surface protein as RTS,S but shows nearly double the efficacy6. This is attributed to its adjuvant, Matrix-M, an immune booster that has been part of influenza vaccines10 and the Novavax COVID-19 vaccine11.
Technological advances may even bring forth mRNA based vaccines against malaria in the future. BioNTech announced the beginning of Phase 1 clinical trials on a mRNA malaria vaccine last month12. The vaccine candidate, BNT165b1, also incorporates part of the circumsporozoite protein, and is part of a program to develop multi-antigen vaccine candidate. More recently, researchers at George Washington University have created two mRNA vaccines, one that targets the parasite’s ability to invade the liver, and one that hinders its ability to reproduce13. When administered together, they were effective in limiting rates of infection and transmission in mice according to their findings published in npj Vaccines.
Ultimately, the more promising vaccine candidates there are, the better.
Multiple vaccines help meet the supply demands required to provide immunity to affected regions of the world and help cater to different demographics (i.e. the elderly, pregnant women, children). Different vaccine formulations will also enable vaccinations in more rural or hard to reach communities. For example, mRNA vaccines require cold storage and transportation which some areas are not well equipped for. Therefore, having vaccines without these requirements will aid in distribution and increasing vaccination rates. A future in which a range of malaria vaccine options are available increases the possibility and hope for eradicating the disease.
References:
1. Cox, F.E. History of the discovery of the malaria parasites and their vectors. Parasites Vectors 3, 5 (2010). https://doi.org/10.1186/1756-3305-3-5
2.“Malaria’s Impact Worldwide .” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 16 Dec. 2021, https://www.cdc.gov/malaria/malaria_worldwide/impact.html
3.“How Can Malaria Cases and Deaths Be Reduced? .” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 7 Oct. 2021, https://www.cdc.gov/malaria/malaria_worldwide/reduction/vaccine.html.
4.Neglected Disease Research and Development: New Perspectives. Policy Cures Research (2021).
5.Undark, Pratik Pawar. “Why Did It Take 35 Years to Get a Malaria Vaccine?” Smithsonian.com, Smithsonian Magazine, 2 June 2022, https://www.smithsonianmag.com/science-nature/why-did-it-take-35-years-to-get-a-malaria-vaccine-180980151/.
6.Mandavilli, Apoorva, and Kang-chun Cheng. “At Long Last, Can Malaria Be Eradicated?” The New York Times, The New York Times, 4 Oct. 2022, https://www.nytimes.com/2022/10/04/health/malaria-vaccines.html.
7.Hogan AB, Winskill P, Ghani AC (2020) Estimated impact of RTS,S/AS01 malaria vaccine allocation strategies in sub-Saharan Africa: A modelling study. PLOS Medicine 17(11): e1003377. https://doi.org/10.1371/journal.pmed.1003377
8.Skerrett, Patrick. “The First Malaria Vaccine Is Here. Let’s Meet the Moment.” STAT, STAT, 7 Oct. 2022, https://www.statnews.com/2022/10/10/first-malaria-vaccine-is-here-lets-meet-the-moment/.
9.Sirima, Sodiomon B., et al. “A Randomized Controlled Trial Showing Safety and Efficacy of a Whole Sporozoite Vaccine against Endemic Malaria.” Science Translational Medicine, vol. 14, no. 674, 2022, https://doi.org/10.1126/scitranslmed.abj3776.
10.Magnusson, Sofia E., et al. “Immune Enhancing Properties of the Novel Matrix-M™ Adjuvant Leads to Potentiated Immune Responses to an Influenza Vaccine in Mice.” Vaccine, vol. 31, no. 13, 25 Mar. 2013, pp. 1725–1733., https://doi.org/10.1016/j.vaccine.2013.01.039.
11.Tribble, S.J, Pradhana, R., Kaiser Health News “Novavax’s Effort to Vaccinate the World, from Zero to Not Quite Warp Speed.” Quartz, 20 July 2021, https://qz.com/2035720/can-novavax-fulfill-its-promise-of-vaccinating-the-world.
12.BioNTech initiates phase 1 clinical trial for malaria vaccine program BNT1652. BioNTech. (2022, December 23). Retrieved January 18, 2023, from https://investors.biontech.de/news-releases/news-release-details/biontech-initiates-phase-1-clinical-trial-malaria-vaccine
13.English, Aidan, and Audrey Scott. “GW Researchers Develop Two Vaccines for Malaria Using MRNA Technology.” The GW Hatchet, 17 Jan. 2023, https://www.gwhatchet.com/2023/01/17/gw-researchers-develop-two-vaccines-for-malaria-using-mrna-technology/.