PIO-led team designs novel vaccine to help fight malaria

A team led by an Indian-origin scientist has designed a new "second generation" malaria vaccine that may offer protection against Plasmodium falciparum parasite, which causes the deadly disease.

Malaria, which infected about 228 million individuals worldwide in 2018, remains a threat to public health and regional stability, according to Sheetij Dutta from the Walter Reed Army Institute of Research (WRAIR) in the US.

Large human populations live in malaria-infested regions of Africa, Southeast Asia and South America, where mosquitoes continuously transmit the malaria parasites from sick to healthy individuals.

Though infection rates have been decreasing, this decline has stagnated in recent years, necessitating novel interventions, according to the study published in the journal PNAS.

 

The first generation malaria vaccine, RTS,S (Mosquirix), is based on the circumsporozoite protein (CSP) of Plasmodium falciparum.

CSP is a secreted protein of the malaria parasite, and is the

target of RTS,S vaccine.

While RTS,S has conferred high level protection in controlled human malaria infection trials, its potency and duration of protection against natural malaria infection needs to be improved, the researchers noted.

In an attempt to develop a second-generation malaria vaccine, Dutta's laboratory at the WRAIR, has used the nano-sized disk and rod shaped particles of the tobacco mosaic virus.

TMV was one of the earliest known viruses that causes mottling of tobacco leaves.

The research shows that the TMV coat protein can also be highly effective as a vaccine scaffold to refocus the host immune system to the most vulnerable epitopes -- part of an antigen molecule to which an antibody attaches itself -- on CSP.

Since the TMV-based malaria vaccine was produced using recombinant DNA technology in bacterial cells, it is non-infectious to humans and will pose no risk to plants, the researchers said.

"The TMV-malaria vaccine showed 10 times improvement over a comparator vaccine in mice, and the superiority of this vaccine was confirmed in Rhesus monkeys," Dutta added.

The researchers found that serum antibodies from the vaccinated monkeys potently blocked parasite entry into human liver cells up to 11 months following vaccine administration.