Close-up of Anopheles mosquito biting a human
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A mRNA vaccine has been created that prevents malaria by generating an immune response in the liver, proving effective even after previous infection in preclinical studies.

It is the first mRNA vaccine to target the liver stage in the life cycle of the plasmodium protozoan, which causes the disease.

The vaccine produces a targeted immune response through T cells in the liver where the parasite grows and develops before infecting red blood cells, according to the findings published in Nature Immunology.

The research demonstrates the widespread potential of RNA technology to solve some of the world’s greatest health issues.

Researcher Lauren Holz, PhD, from the University of Melbourne in Australia, highlighted the ability of the mRNA vaccine to provide protection even after existing exposure to malaria.

“This is important because many vaccines undergoing trials fail in areas where the disease is endemic and exposure is widespread, so the fact that our vaccine still works after prior exposure is very encouraging,” she told Inside Precision Medicine.

“The hope is that we can move this vaccine from the bench to the clinic and put a major dent in the significant morbidity and mortality associated with malaria.”

Deaths from malaria are rising each year, according to the World Health Organization, and creating a highly effective vaccine remains a major goal. In 2020, there were more than 240 million malaria cases, leading to well over 620,000 deaths.

More than three quarters of these deaths were among children aged less than 5 years, equating to nearly one every minute.

Typically, a traditional-style vaccine will work by looking for antigens on the surface of the pathogen and produce antibodies that can offer long-term, effective immunity. However, this approach is less effective for malaria as the parasite hides in cells that antibodies cannot reach.

The researchers initially investigated a peptide-based malaria vaccine that contained only small fragments of a malaria protein but by 2018 had moved on towards investigating RNA vaccines.

The mRNA vaccine they have created encodes an entire malaria protein, which theoretically could create a broader and more protective response from the immune system.

Whereas the COVID-19 vaccine operates by neutralizing antibodies, the mRNA malaria vaccine produces a targeted response through T-cells in the immune system.

A standard mRNA vaccine was neither able to generate liver tissue-resident memory T cells, nor able protect mice against challenge with the sporozoite stage of Plasmodium berghei.

However, adding an agonist originally developed for cancer immunotherapies enabled the recruitment of T cell help from type I natural killer T cells.

This creating a localized vaccine response in the liver, targeting and stimulating specific immune cells where the parasite first travels to develop and mature after entering the bloodstream.

Researcher Gavin Painter, PhD, a professor at Victoria University of Wellington, New Zealand, told Inside Precision Medicine: “These findings show T cell immunity can be generated in the liver with mRNA vaccine, and it protects against challenge.

“It’s clinically relevant because mRNA vaccines have proved extremely versatile and amenable to scale up and widespread production compared to traditional vaccine formats.”

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