New long-lasting vaccine for malaria shows promise

Scientists have developed a new long-lasting vaccine that protects mice against malaria, a disease that about 3.2 billion people are currently at risk of contracting.
Researchers from the Institut Pasteur, the CNRS (French National Centre for Scientific Research) and Inserm (French Institute of Health and Medical Research) have experimentally developed a live, genetically attenuated vaccine for Plasmodium, the parasite responsible for the disease.
By identifying and deleting one of the parasite's genes, the scientists enabled it to induce an effective, long-lasting immune response in a mouse model.
Despite increased prevention and eradication efforts over the past fifteen years, especially targeting mosquito vectors, malaria remains the parasitic disease that poses the biggest threat for the world's population.

About 214 million cases and 438,000 deaths from malaria were recorded in 2015, mostly children under the age of five and pregnant women.
An effective vaccine is needed to combat this disease, but the complex biological make-up of Plasmodium and the many strategies the parasite has evolved to outmanoeuvre the host immune response mean that developing a malaria vaccine is a difficult task.

One notable feature of patients infected by the malaria parasite is the difficulty in mounting a long-lasting protective immune response.
Premunition, or relative immunity, is only acquired after several years of exposure. An important feature during malaria infection is that the parasite prevents the establishment of immunological memory.

Scientists genetically modified strains of the Plasmodium parasite by deleting the gene that codes for the HRF (histamine-releasing factor) protein.
The resulting mutants, which no longer expressed HRF, proved to be highly effective in triggering a potent immune response.
The absence of HRF boosted the production of the IL-6 cytokine, known for its ability to stimulate the immune response, in the liver and the spleen.
This conferred mice with protection from any potential reintroduction of the Plasmodium parasite, including highly virulent strains.
This protection was long lasting as it was maintained for more than a year, suggesting that a long-term immunological memory had been established. The protection was also effective against all stages of the parasite's life cycle.

The HRF mutants obtained in this study are the first genetically modified parasites whose mutation has a direct impact on the host's immune response.
Use of this target gene, or a similar strategy to stimulate immunity, could lead to the development of effective, long-lasting live vaccines for malaria.
These findings were published in the Journal of Experimental Medicine on July 18, 2016.