Malaria Vaccine Development: Current Status and Future Prospects

Status Update

Malaria Vaccine Update: Global Disease Burden and Vaccination Milestones
Update (March 4, 2025 | 11:29 AM)
 
Many thanks to David Trent of the World Animal Foundation for prompting an update on the global burden of malaria.
 
According to data published by the World Health Organization (WHO) on December 11, 2024, the estimated number of malaria cases worldwide increased to 263 million in 2023, up from 252 million in 2022, indicating a modest rise in global incidence.
 
Encouragingly, estimated malaria-related deaths declined slightly, from approximately 600,000 in 2022 to 597,000 in 2023. Whether this reduction is statistically significant remains unclear. Nonetheless, these figures highlight that malaria continues to impose a substantial global health burden.
 
Taken together, the data underscore the urgent need to improve malaria vaccines, expand equitable access to vaccination, and sustain complementary preventive measures such as mosquito control, chemoprophylaxis, and early diagnosis.

Historic Milestone: Routine Childhood Malaria Vaccination Begins
 
After more than 60 years of malaria vaccine research and development, a historic milestone was reached on January 22, 2024, when routine childhood malaria vaccination was officially launched in Cameroon.
 
On that date, infants and toddlers received RTS,S/AS01 (Mosquirix)—the first malaria vaccine recommended by the WHO in 2021—as part of the country’s standard childhood immunization schedule. This marked the first time in history that a malaria vaccine was deployed for routine use at the national level.
 
The milestone was widely reported in international media, including Reuters, which described the event as a global public health breakthrough:
 
“Cameroon begins routine malaria shots in global milestone.”
— Reuters, January 22, 2024, 5:59 PM EST

Introduction
 
For most people in Western countries, malaria only becomes a concern when planning travel to regions where the disease is endemic and widespread. A natural first question is whether a malaria vaccine is available. Unfortunately, as of today, no malaria vaccine has been approved by the U.S. Food and Drug Administration (FDA), and there are no pending FDA reviews. This situation is similar across most Western regulatory jurisdictions.
 
As a result, travelers to malaria-endemic regions must still rely on prophylactic antimalarial medications (1), such as atovaquone–proguanil (Malarone), chloroquine phosphate (Aralen), mefloquine, primaquine, tafenoquine (Arakoda™), or doxycycline. These drugs differ in mechanism of action, dosing schedules, side-effect profiles, and suitability depending on an individual’s health status, and must be prescribed by a healthcare professional.
 
In addition to medication, preventive measures—including daytime use of mosquito repellents, wearing protective clothing, and sleeping under insecticide-treated bed nets—remain essential.
 
Despite these limitations, there is encouraging progress. Two malaria vaccines have now been recommended by the World Health Organization (WHO) for use in children in sub-Saharan Africa and other regions with moderate to high malaria transmission. These vaccines represent the culmination of decades of challenging research and development (2). While they are not yet approved for travelers, there is hope that continued data collection may eventually support broader regulatory approval.

Malaria: Disease Background and Global Burden
 
Malaria is a mosquito-borne parasitic disease characterized by recurrent fever, chills, sweating, anemia, and—if left untreated—potentially fatal complications. It is caused primarily by Plasmodium falciparum and Plasmodium vivax parasites and transmitted by female Anopheles mosquitoes.
 
Malaria remains a major global health challenge. According to the World Health Organization, an estimated 247 million malaria cases and 619,000 deaths occurred worldwide in 2021, with 95% of cases and 96% of deaths concentrated in the WHO African Region (3).
 
Transmission intensity varies depending on environmental factors such as temperature, rainfall, and humidity, as well as mosquito ecology and human behavior. Malaria risk can change over time as control measures are introduced or withdrawn. Effective strategies—such as insecticide-treated bed nets, indoor residual spraying, and antimalarial therapies—have reduced malaria in some regions, while others remain highly vulnerable.
 
Travelers should always consult the most up-to-date malaria risk information, including the CDC malaria distribution map (4) and the WHO malaria threat map (5), before visiting endemic areas.

WHO-Recommended Malaria Vaccines
 
RTS,S/AS01 (Mosquirix)
 
RTS,S/AS01, marketed as Mosquirix, is the first malaria vaccine ever approved for use. Developed by the Walter Reed Army Institute of Research and GlaxoSmithKline (6), it received a WHO recommendation in 2021 (7).
 
The vaccine requires four doses and has demonstrated approximately 40% protection against clinical malaria and 30% protection against severe malaria over a four-year period⁷.
 
Mosquirix targets the circumsporozoite protein (CSP) of Plasmodium falciparum, a key surface antigen involved in liver infection. The vaccine also incorporates a hepatitis B surface antigen to enhance immune response and provide dual protection. It is a recombinant protein vaccine produced in genetically engineered yeast cells (8,9).
 
R21/Matrix-M
 
R21/Matrix-M is the second malaria vaccine to receive a WHO recommendation, announced in 2023 (10). Developed by the University of Oxford and the Serum Institute of India, it uses Novavax’s Matrix-M adjuvant technology.
 
R21/Matrix-M is the first malaria vaccine to meet the WHO target of at least 75% efficacy. In clinical trials, it reduced symptomatic malaria cases by approximately 75% during the first year after vaccination (11). The vaccine requires three doses.
 
Like RTS,S, R21 targets the CSP antigen of P. falciparum, but differs in formulation and adjuvant design—an approach previously validated in Novavax’s COVID-19 vaccine.

Current Applications and Regulatory Status
 
Neither RTS,S/AS01 nor R21/Matrix-M has been approved or authorized by the FDA for use in the United States. The FDA applies different regulatory standards and considers domestic public health need when evaluating vaccines. Since malaria is not endemic in the U.S. and most cases are travel-related, regulatory approval for general use has not been prioritized.
 
These vaccines are primarily intended for children and pregnant women in high-burden regions, where malaria remains a leading cause of morbidity and mortality. As of now, at least 28 African countries plan to introduce WHO-recommended malaria vaccines into their national immunization programs.
 
Gavi, the Vaccine Alliance, supported by the Bill & Melinda Gates Foundation, has approved funding to support malaria vaccine rollout in 18 countries (12). According to WHO timelines, RTS,S is becoming available in select African countries in early 2024, while R21 is expected to follow in mid-2024.

Future Prospects in Malaria Vaccine Development
 
A fully protective malaria vaccine has yet to be achieved. Ongoing research efforts are focused on:

• Improving the efficacy and durability of RTS,S and R21
• Developing novel antigen–adjuvant combinations
• Exploring attenuated sporozoite vaccines
• Addressing parasite genetic diversity and mutation potential (13)

While scientific and logistical challenges remain, progress continues. The Bill & Melinda Gates Foundation has articulated a long-term vision to eradicate malaria by 2040 (14), while the WHO has set a more ambitious goal of ending the global malaria threat by 2030 (15).
Although ultimate success is not guaranteed, the rapid advances seen over the past decade provide strong reasons for cautious optimism.

References
 
[1] CDC-Choosing a Drug to Prevent Malaria
[2] Amal A. El‑Moamly and Mohamed A. El‑Sweify. Malaria vaccines: the 60‑year journey of hope and final success—lessons learned and future prospects. Trop. Med. & Health (2023) 51:29. https://doi.org/10.1186/s41182-023-00516-w.
[3] World Malaria Day 2023/ Malaria by numbers: global and regional burden
[4] CDC-Where Malaria Occurs
[5] WHO-Malaria Threats Map: tracking the spread of biological threats to malaria
[6] WHO grants prequalification to GSK’s Mosquirix – the first and only approved malaria vaccine
[7] CDC-Malaria vaccine recommended for broader use by WHO: “Best thing since bed nets”
[8] Matthew B. Laurens. RTS,S/AS01 vaccine (Mosquirix™): an overview. Human Vaccines & Immunotherapeutics (2020) 16, 480-489. https://doi.org/10.1080/21645515.2019.1669415
[9] Yahiya Y. Syed. RTS,S/AS01 malaria vaccine (Mosquirix®): a profle of its use. Drugs & Therapy Perspectives (2022) 38:373–381. https://doi.org/10.1007/s40267-022-00937-3
[10] WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization
[11] Mehreen S Datoo, Magloire H Natama, et al. Efficacy of a low-dose candidate malaria vaccine, R21 in
adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. The Lancet (2021) 397, 1809-1818. https://doi.org/10.1016/S0140-6736(21)00943-0
[12] Gavi outlines plans to build sustainable supply of malaria vaccines
[13] Wikipedia> Malaria vaccine
[14] Report by UN and Gates Foundation presents vision for eradicating malaria by 2040
[15] “A great day for science”: WHO recommends second vaccine against malaria