A step closer to producing an efficient, broad-based malaria vaccine
The Hindu
Scientists have identified as small segment of malarial parasite protein that has the potential to prevent malaria caused by different species and strains of Plasmodium.
In a recent breakthrough to combat malaria, scientists at the Tate Institute of Fundamental Research (TIFR), Mumbai and the University of Maryland School of Medicine, Baltimore, U.S. have identified a small segment of malarial parasite protein that has the potential to be used as a broad-based vaccine to prevent malaria caused by different species and strains of Plasmodium. In addition to preventing malaria in humans, the small segment of protein has the potential to block transmission in mosquitoes. The results were published recently in Malaria Journal.
The protein, enolase, is normally found inside parasites and host cells and is involved in burning glucose to produce energy, which is fundamental for the survival of a cell. But scientists found the protein on the outer surface of the parasites in two invasive stages — merozoites that invade the red blood corpuscles (RBCs) of humans and the ookinetes that invade the gut wall of mosquitoes.
“This is an unusual event and there must be some functional reason for being present on the outer surface of the parasite,” said Gotam K. Jarori from the Department of Biological Sciences, TIFR and one of the corresponding authors of the paper. “The molecule is important for invading the host cells and multiplying.”
In animal studies, antibodies against the protein were produced when it was injected into mice. Compared with the controls, the mice that were immunised before being challenged survived for a longer duration. “Normal mice died within 5-6 days after parasite injection, while immunised mice survived on average 10-11 days. Some survived beyond 12 days,” Dr. Jarori said.
Though the parasite protein is largely similar to human molecule, the scientists found a small portion (five amino acid) of the parasite protein, which is unique to parasite enolase and is absent in human enolases, has protective antigenic properties. This unique segment was genetically stitched to a nanoparticle protein and this hybrid protein was used for vaccinating mice.
“Since enolase is implicated in invasion of RBCs in human hosts as well as the gut wall of mosquitoes, antibodies against this small fragment can potentially have a dual benefit by blocking the multiplication cycle of the parasite in humans, as well as inhibiting transmission through mosquitoes,” Dr. Jarori said.
“The reason why we call it as broad-based molecule against malaria is because the five amino acid segment is conserved in different species of malaria parasite,” he said.
According to Sneha Dutta, a graduate student at TIFR who conducted these experiments and is one of the authors, the small segment is present in all human malaria causing species of Plasmodium and hence, antibodies directed against it are likely to protect against all species of the parasite. The researchers also found that the small segment is highly conserved in different strains so will be effective against all strains.
Unlike the vaccine candidate being developed by TIFR, the vaccines that are currently being tested specifically target certain species or strains and are not broad-based.
Since the small segment plays a very crucial of burning glucose to produce energy, there cannot be any mutation to bypass the immune system. Hence any vaccine developed to target the conserved segment will remain effective even after prolonged period of usage.
According to him, though antibody titter was not very high, protection was observed, though only partial. “We can enhance the antibody protection using adjuvant,” he said.
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