Since HHS Secretary Robert F Kennedy Jr is ending Federal support for mRNA-based vaccines, I thought I would focus on lifesaving ones like the malaria vaccine.

Malaria is a deadly disease that kills several hundred thousand people a year, and a safe and effective vaccine for the disease has been a goal for researchers for many years.

Using mRNA-based vaccine technology, researchers are taking novel approaches in developing new vaccines against malaria.

This article will review the disease and the early studies on mRNA vaccines for malaria.

All about malaria

Malaria is caused by a single-celled parasite from one of four related microorganisms in the Plasmodium group. It is carried to humans by an infected female Anopheles mosquito.

Malaria infection develops through two phases – one that involves the liver (exoerythrocytic phase) and one that involves red blood cells, or erythrocytes (erythrocytic phase). When an infected mosquito pierces a person’s skin to take a blood meal, malaria sporozoites in the mosquito’s saliva enter the bloodstream and migrate to the liver, where they infect liver cells, multiplying asexually and asymptomatically for 8–30 days.

After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which, following the rupture of their host cells, escape into the blood and infect red blood cells, beginning the erythrocytic stage of the malaria life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.

Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade new red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.

Malaria symptoms include chills, flu-like symptoms, fever, vomiting, diarrhea, and jaundice. It can be life-threatening if untreated.

Speaking of treatments, malaria is treated with antimalarial medications – the one used depends on the type and severity of the disease.

One of the best methods to prevent malaria is to destroy the mosquito vector; however, this brings with it several environmental issues. There is ongoing research on a genetically modified mosquito that basically ends the parasite/mosquito life cycle, but we are a long way from that being widely implemented.

Malaria is endemic in tropical areas worldwide, including Sub-Saharan Africa, South America, and Asia. However, it was once prevalent in other areas, such as Southern Europe and the Southern USA, until post-World War II eradication efforts, including the use of the environmentally hazardous DDT, eliminated it in those regions.

In 2023, the World Health Organization reported that there were 263 million cases of malaria and 597,000 deaths from malaria across 83 countries. Most of the cases and deaths occurred in tropical and subtropical areas. Although malaria is no longer endemic in the USA and other northern countries, it was once here, and it could return with the warming climate that could increase mosquito populations.

GlaxoSmithKline’s malaria vaccine RTS, S/AS01 (RTS, S), has been approved by the European Medicines Agency. Unfortunately, it is only moderately effective, around 26-50% in children.

Another vaccine in development has shown high effectiveness and safety in early clinical trials.

Malaria mRNA vaccines research

In a study published on 28 June 2025 in Vaccines (Basel), James M Burns Jr, Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, and colleagues, compared the immunogenicity and efficacy of the PyMSP1/8-sec mRNA vaccine versus the recombinant formulation in outbred mice.

The researchers found that the mRNA vaccines were highly immunogenic and potently protective against blood-stage malaria, outperforming a similar recombinant-based vaccine. 

Obviously, this study was a preclinical trial in mice, so we would need to see if the vaccine was safe and effective in humans, but it is an exciting start. The researchers could target specific antigens on the surface of the Plasmodium parasite, making it more effective than other recombinant vaccines, which have lower specificity to the parasite’s antigens.

In another study from Australia, researchers The research revealed the critical contact points for Plasmodium fertilization, which could be a target for a new vaccine.

Building on the structural discovery, the team designed a next-generation mRNA vaccine. In preclinical studies, the vaccine triggered high levels of antibodies that recognised the parasite and blocked transmission in mosquitoes by up to 99.7%.

Uniquely, this vaccine works inside the mosquito, where sexual reproduction of the parasite occurs. So when the mosquito bites an immunized person, antibodies enter the mosquito, preventing the Plasmodium from reproducing and thereby reducing transmission.

Again, this research is very early stage, and we are years from it being shown to be safe and effective in humans.

Summary

As you can see, the research on mRNA vaccines for malaria is in very early stages. But this is the kind of basic research that would be supported by funding that was cut by RFK Jr.

I know some of you might think that malaria is not a disease that endangers your life, but that’s not the point. Vaccine research is not just for Americans or Norwegians or Australians; it is meant for the whole world.

A safe and effective mRNA-based malaria vaccine will save hundreds of thousands of lives across the world. And given our world’s inability to halt climate change, malaria might be coming to your hometown someday soon.

But there’s more to this type of research. Scientists often search for results in one area, which leads to innovations in another. Who knows if this basic research on vaccines for malaria will lead to a breakthrough that can be applied to another disease, like norovirus or cancer?

Hopefully, other countries will continue the research into an mRNA-based malaria vaccine. The world needs another vaccine that saves lives.

Citations

• Bledsoe GH. Malaria primer for clinicians in the United States. South Med J. 2005 Dec;98(12):1197-204; quiz 1205, 1230. doi: 10.1097/01.smj.0000189904.50838.eb. PMID: 16440920.
• Dietrich MH, Chmielewski J, Chan LJ, Tan LL, Adair A, Lyons FMT, Gabriela M, Lopaticki S, Dite TA, Dagley LF, Pazzagli L, Gupta P, Kamil M, Vaughan AM, Rojrung R, Abraham A, Mazhari R, Longley RJ, Zeglinski K, Gouil Q, Mueller I, Fabb SA, Shandre-Mugan R, Pouton CW, Glukhova A, Shakeel S, Tham WH. Cryo-EM structure of endogenous Plasmodium falciparum Pfs230 and Pfs48/45 fertilization complex. Science. 2025 Jul 31:eady0241. doi: 10.1126/science.ady0241. Epub ahead of print. PMID: 40743371.
• Ott AC, Loll PJ, Burns JM Jr. An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal Plasmodium yoelii. Vaccines (Basel). 2025 Jun 28;13(7):702. doi: 10.3390/vaccines13070702. PMID: 40733679; PMCID: PMC12300687.

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