The Story of Bacteria and Vaccines in the Fight Against Malaria

Author: Dr. Dipika Mishra. I hold a Ph.D. degree in Life Sciences from the National Institute of Science Education and Research (NISER) and am a SciCom enthusiast (eLife Community Ambassador for the year 2019-2020).

In tropical and sub-tropical countries across the globe, myriad human lives are lost due to the bite of a mosquito. As per the latest World malaria report, there are currently 247 million cases of malaria worldwide and 619,000 people die due to malaria each year. Further, infants under the age of five are majorly affected by this mosquito-borne disease. To curb the menace of malaria parasites, insecticides have been majorly used. However, the rampant rise in insecticide-resistant malaria parasites and the diminished efficiency of vaccines have compelled researchers to look for alternative strategies. The search for solutions to this problem has led researchers to generate genetically engineered microbes in the past. Nonetheless, bacteria with the inherent ability to counter malaria parasites had never been identified. As per a recent study published in the journal Science (https://doi.org/10.1126/science.adf8141), researchers have identified a species of bacterium Delftia tsuruhatensis TC1 inside the mosquito gut that disrupts the growth of the malaria parasite. Furthermore, recently, WHO has recommended the use of a new malaria vaccine called R21/Matrix M developed by Oxford University and the Serum Institute of India. Both these findings are potent weapons in the war against malaria.

Harmane-the compound that kills malaria parasite

Female Anopheles mosquitoes are the carriers of the malaria parasite Plasmodium. Malaria is transmitted between humans when a female Anopheles mosquito bites an individual infected with the malaria parasite. The malaria parasite Plasmodium develops into the next stage in the mosquito gut before being finally released into its salivary glands. From the salivary glands, the parasite is ready to venture into a new host once the mosquito bites another individual. The bacterium Delftia tsuruhatensis TC1 majorly targets the parasite in the gut and affects the development of the Plasmodium parasite by producing a small molecule inhibitor called “harmane.”

Harmane is a hydrophobic compound that was first isolated from Arariba rubra and is majorly found in plant extracts, a variety of food, and mammalian body fluids. It also serves as an active ingredient in many traditional medicines. The results of the study demonstrate that harmane does not inhibit the asexual phase of the parasite but mainly targets the sexual phase of the parasite i.e., the ookinetes. This compound is highly effective against Plasmodium. Furthermore, harmane has the ability to penetrate the cuticle of mosquitoes and thus has potential therapeutic uses for treating malaria.

The field trials to test the effect of the bacterium on the Plasmodium parasite were conducted in Burkino Faso which is a 10-meter by 10-meter by 5-meter enclosure designed to emulate the real world with plants and breeding areas. The cotton balls soaked in sugar and D. tsuruhatensis were left in the enclosure overnight. Following this, the bacterium inhibited the malaria parasite. This was evident when the mosquitoes fed on the blood of people infected with malaria, the bacterium inhibited the development of the parasite. This result was similar to the lab findings and thus proved that the microbe was efficient in preventing parasite development.

The Malaria Vaccine

R21/Matrix M vaccine is the second malaria vaccine approved by WHO following the approval of the first malaria vaccine RTS,S/AS01 or Mosquirix in 2021. R21/Matrix M is a sub-unit vaccine that contains the circumsporozoite protein from P.falciparum. The circumsporozoite protein mainly coats the surface of the parasite. The use of circumsporozoite protein in the vaccine enables the recognition and subsequent immune response against the malaria parasite, thus killing the parasite prior to infection. Also, both these vaccines have a scaffold of malaria antigen and Hepatitis B virus surface antigen. In contrast to the RTS,S vaccine wherein one in five molecules has an antigen fused to it, each molecule of the R21 vaccine has a fused antigen, thus ensuring the effectiveness of the new malaria vaccine. Furthermore, both these vaccines are provided with an adjuvant i.e., constituents that improve immune response against the antigen. Similar to RTS,S, the new malaria vaccine is also administered in three doses and a booster dose 12 months after the third jab. Moreover, R21 is very potent as each dose has 5 µg of the antigen as against 25 µg in the case of RTS,S.

Future Perspectives

This is not the first study of using microbes to fight malaria. Wolbachia pipientis had been earlier used to treat Dengue. However, Wolbachia was not a natural occupant of the Aedes aegypti mosquitoes (carrier of Dengue virus) and thus had to be artificially introduced into the mosquitoes in the laboratory. Further, genetically engineered microbes have also been used to target Plasmodium. Notably, this is a novel study of a naturally occurring bacterium that has the potential to target the parasite and stop malaria transmission. Furthermore, studies on the molecule harmane and its potential therapeutic uses in mosquito nets and breeding sites can further reduce the menace of malaria. Apart from the gut of mosquitoes, Delftia tsuruhatensis TC1 also resides in the guts of certain insects and is also found in water and soil.  Thus, studies on the effect of the bacterium on other creatures need to be undertaken.

Further, the new vaccines rekindle the hope of fighting the malaria parasite in tropical countries across the globe. However, the vaccine must be used along with other protection measures against malaria. In the current scenario where mosquitoes are rapidly evolving to gain resistance against insecticides, these new discoveries, one on the microbe and the other vaccine, tend to add an important weapon to the human arsenal against malaria.