US researchers have identified an antigen that generates antibodies to hinder the ability of malaria parasites to multiply, an advancement that could lead to the development of a malaria vaccine.
The discovery of the antigen, known as PfSEA-1, is a critical addition to the limited pool of antigens currently used in candidate malaria vaccines, the researchers reported Thursday in the US journal Science.
An estimated 627,000 people die from malaria each year according to the World Health Organization, with most deaths from the mosquito-borne parasitic disease occurring among young children living in sub-Saharan Africa.
People who live in areas where malaria is common frequently develop protective immune system responses that can limit malaria parasite levels in the blood and prevent the high fever and illness associated with malaria infection.
Using plasma samples from 2-year-old Tanzanian children who were either resistant or susceptible to malaria infection, researchers performed gene-screening experiments and a series of laboratory tests that identified PfSEA-1.
Multiple tests confirmed that antibodies to PfSEA-1 halted malaria infection at the point when the parasite leaves one red blood cell to invade a new one, which may protect against severe malaria infection.
"Many researchers are trying to find ways to develop a malaria vaccine by preventing the parasite from entering the red blood cell, and here we found a way to block it from leaving the cell once it has entered," said Jonathan Kurtis, director of the Center for International Health Research at Rhode Island Hospital, and the study's principal investigator. "If it's trapped in the red blood cell, it can't go anywhere .. it can't do any further damage. "
The researchers then vaccinated five groups of mice with the novel antigen to evaluate its effects after the mice were exposed to malaria.
In all groups, the vaccinated mice had lower levels of malaria parasites and survived longer than the unvaccinated mice.
The researchers also measured antibody levels in plasma samples from 453 Tanzanian children from the previous cohort and discovered that no cases of severe malaria occurred during periods when the children had detectable antibodies to PfSEA-1.
Further, they evaluated plasma samples from 138 males aged 12 to 35 living in a malaria-endemic area of Kenya and found that individuals with detectable antibodies to PfSEA-1 had 50 percent lower parasite densities compared to individuals with no detectable antibodies.
Kurtis said that they will conduct additional trials on PfSEA-1, first in another animal model, and then they hope to begin Phase I trials in humans "very soon."
"Our findings support PfSEA-1 as a potential vaccine candidate, " said Kurtis. "We are confident that by partnering with our colleagues at the National Institutes of Health and other researchers focused on vaccines to prevent the parasites from entering red blood cells, we can approach the parasite from all angles, which could help us develop a truly effective vaccine to prevent this infectious disease that kills millions of children every year."
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