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Parasite-Blocking Antigen Discovery May Lead To Malaria Vaccine

May 23, 2014
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Lawrence LeBlond for redOrbit.com – Your Universe Online

Malaria remains a dangerous disease in the developing world, killing more than 627,000 people a year, according to the World Health Organization (WHO). Because most deaths associated with malaria occur in children in Sub-Saharan Africa, finding a vaccine against the deadly virus is all too important.

New research, by a team from Rhode Island Hospital (RIH), has uncovered a protein, or antigen, that is essential for malaria-causing parasites to escape from red blood cells. This protein also generates antibodies that can hinder the ability of malaria parasites to multiply, which may protect against severe malaria infection.

This antigen, known as PfSEA-1, was associated with reduced parasite levels among children and adults in malaria-endemic areas. An investigational vaccine was developed using the antigen and when exposing mice to this antigen, the rodents experienced lower malaria parasite levels.

This discovery could be a critical addition to the limited number of antigens that are currently being used in candidate malaria vaccines. The study findings, published in the journal Science, results from a collaboration of scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and NIAID grantees.

“This research really began in 2002 when our colleagues from the National Institutes of Health, led by Patrick Duffy and Michal Fried, enrolled a birth cohort of children in Tanzania,” said lead author Jonathan Kurtis, MD, PhD, director of the Center for International Health Research at RIH. “Six years ago we began using these samples to identify novel vaccine candidates and now it’s coming full circle. While a portion of this research was conducted in mice, the actual vaccine discovery experiments were performed using human samples, thus we believe the results will effectively translate to humans.”

In the mouse experiments, the team conducted five independent vaccine trials in which they were vaccinated with the novel PfSEA-1 (Schizont Egress Antigen-1). All mice were then injected with malaria parasites. In all five experiments, the vaccinated mice had lower levels of parasites and survived much longer than the unvaccinated group.

“When my post-doctoral fellow Dipak Raj discovered that antibodies to this protein, PfSEA-1, effectively trapped the malaria-causing parasite within the red blood cells, it was truly a moment of discovery,” Kurtis said. “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. If it’s trapped in the red blood cell, it can’t go anywhere… it can’t do any further damage.”

Kurtis and colleagues then measured antibodies to PfSEA-1 in the entire Tanzanian birth cohort of 785 children. They found that among children with antibodies to PfSEA-1, there were zero cases of severe malaria.

The team then went back to a serum bank they had collected from 140 children in Kenya in 1997. They found that the children who had antibodies to PfSEA-1 in this group had 50 percent lower parasitemea than those without the antibodies during a high transmission season.

“Our findings support PfSEA-1 as a potential vaccine candidate, and 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,” Kurtis said in a statement.

The researchers said the results were encouraging, but stressed that more research was required before human trials could begin.

“I am cautious. I’ve seen nothing so far in our data that would cause us to lose enthusiasm. However, it still needs to get through a monkey study and the next phase of human trials,” Kurtis told BBC News.

This study adds to the growing body of work being explored in the race to find a malaria vaccine.

The RTS,S vaccine, developed by GlaxoSmithKline, is one of the more advanced vaccine candidates being pushed for regulatory approval after Phase III clinical trials showed that the drug almost halved the number of malaria cases in young children and in infants reduced the number of malaria cases by 25 percent.

“The identification of new targets on malaria parasites to support malaria vaccine development is a necessary and important endeavor,” Dr Ashley Birkett, director of the PATH Malaria Vaccine Initiative, said in a comment following the latest study.

“While these initial results are promising with respect to prevention of severe malaria, a lot more data would be needed before this could be considered a leading vaccine approach – either alone or in combination with other antigens,” he said in an interview with the BBC.


Source: Lawrence LeBlond for redOrbit.com - Your Universe Online



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