Indian scientists experimenting with a novel vaccine candidate against malaria say they have found “promising results” in mice, with “80 to 85 per cent efficacy” observed in a dozen animals they recently vaccinated.
The new vaccine candidate, created by a team at the Indian Institute of Science (IISc), contains live malaria sporozoites (an immature stage of the parasite Plasmodium berghei ) with an important genetic modification. The researchers knocked out a gene that produces “heme,” a molecule central to the pathogen’s survival. The vaccine targets the pathogen as it enters the liver, the first destination in the host.
Modus operandi
INSA Senior Scientist, Department of Biochemistry, IISc, G. Padmanabhan, who leads the research at P.N. Rangarajan’s laboratory in the Department of Biochemistry, said that the vaccine candidate appeared to prime the immune system of the mice against the disease, most likely by kickstarting a T cell immune response.
These results are, however, yet to be published, he said.
“We need to repeat the experiment in a few more animals to confirm our results first,” said Viswanathan Arun Nagaraj, a Ramanujan Fellow IISc, and part of the team working on the vaccine. They will next conduct safety trials on their animal models, he added.
The premise of the vaccine — containing mutant, inactivated sporozoites (or genetically attenuated sporozoites) — draws from two critical discoveries made earlier by the same team. The first discovery, made 20 years ago, was that the parasite can produce its own “heme” to sustain itself (although it also draws the molecule from the host’s haemoglobin when the parasite finally colonises in the host’s blood stream).
Second breakthrough
In 2013, the team made its second breakthrough when it identified all the heme-producing genes and found that the parasite’s ability to manufacture heme on its own was essential in its earliest “human stage” — when it enters the host’s liver.
“Inactivating the sporozoites is always the main challenge while researching a malaria vaccine,” Prof. Padmanabhan said. By knocking out one of the heme-producing genes — ALA synthase gene — the researchers essentially created a parasite that was no longer capable of surviving in the liver, let alone being released in exponential numbers into the host’s bloodstream where it manifests as malaria.
“The heme-biosynthetic pathway could be a target for antimalarial therapies in the mosquito and liver stages of infection. The knockout parasite could also be tested for its potential as a genetically attenuated sporozoite vaccine,” Dr. Nagaraj and coauthors had anticipated in a paper published in PLoS Pathogens journal last year.
A vaccine against malaria has been a longstanding research problem especially because drugs have proved inadequate against the parasite that often develops resistance, Dr. Nagaraj said. “Only recently did we have reports from Cambodia of the parasite developing resistance to artemisinin, the most important anti-malaria drug. The parasites are developing resistance to even combination drugs.”
Among the vaccine candidates under various stages of trial around the world is the RTS,S vaccine based on a protein from the malaria sporozoite, which has shown a 30 to 50 per cent efficacy in human trials. Another vaccine being tested uses attenuated irradiated (weakened) sporozoites.
According to the WHO, malaria infected 207 million people across the world in 2012 and killed 627,000 people; nearly 80 per cent of the deaths were of children under five years of age.
