DNA Fingerprinting Throws Doubt on Glaxo Malaria Vaccine Effortby
Malaria is like flu, with thousands of strains, study shows
Strain theory suggests shots must be 100% efficacious to work
Groundbreaking research has shown the potentially deadly malaria parasite has greater genetic diversity than scientists previously understood, a finding that throws doubt on the efficacy of vaccines in development by companies such GlaxoSmithKline Plc.
A study involving more than 600 children from a single village in the West African nation of Gabon found that each had malaria caused by a different strain of the Plasmodium parasite -- or a different composite of as many as 60 genes.
The research, published Tuesday in the Proceedings of the National Academy of Sciences, is the first to rely on DNA fingerprinting to show how malaria’s genetic diversity enables it to evade the human immune system and establish a chronic infection.
The results suggest that scientists need to rethink their approach to malaria vaccines, since full immunity against all strains is needed to halt the disease, which kills more than 400,000 people worldwide. The global malaria vaccines market will exceed $591.8 million by 2024, Coherent Market Insights said in a report last month. The field, led by London-based Glaxo, has been supported by the Bill and Melinda Gates Foundation for more than a decade.
“It’s turning the theory of malaria control on its head -- that’s the important implication,” said Karen Day, who was the first author on the paper, in a telephone interview from Melbourne. “At the moment, we treat malaria like it’s measles, but think that you can get it again and again because of a lack of immunity.”
Day’s research was funded by the National Institutes of Health and involved scientists from the University of Melbourne, the University of Chicago and teams from the Netherlands and France. The group found that the malaria parasite swaps genes during sex to create new variants that can evade the immune system and re-infect the same people, much like influenza can.
The finding of distinctly different strains in infected children -- as many as 10 at once -- means that even small human populations in malaria-endemic areas are constantly being infected with the parasite, said Day, a professor of population science and dean of science at the University of Melbourne. Africa has 90 percent of the world’s malaria cases and 92 percent of malaria deaths, according to the World Health Organization.
“Malaria is a like flu, but much more complicated,” she said. “There are hundreds, if not thousands, of different strains.”
Just as no one flu shot can prevent repeated bouts of the viral illness, there is no malaria vaccine available that can protect against all strains. Studies on Glaxo’s Mosquirix malaria vaccine in 2011 and 2012 showed that a three-dose regimen can reduce by as much as half the number of cases in children, though protection waned over time.
More than 20 other vaccine constructs are being evaluated in clinical trials or are in advanced preclinical development, the Geneva-based WHO said last May, when it announced that Mosquirix should be studied further in sub-Saharan Africa as a “complementary malaria control tool that could potentially be added to -- and not replace -- the core package of proven malaria preventive, diagnostic and treatment measures.”
“Finding ways to overcome the malaria parasite’s defense mechanism is extraordinarily challenging,” said Bernadette Murdoch, a Glaxo spokeswoman in Sydney. “For three decades with our partners we have been developing what could be the world’s first vaccine to help protect children in Africa against malaria.”
“The holy grail would be a vaccine that works against all strains,” Day said. “If you don’t have something that’s 100 percent effective, the system is so diverse, it can persist and bounce back to pre-control levels.”
She presented a strain theory for malaria more than 20 years ago, but failed to change conventional thinking on the ancient scourge.
Day’s latest publication was delayed three years because of her relocation from New York University, and Hurricane Sandy in late 2012, which caused a power outage on the university’s Downtown campus that led to the loss of the project’s genetic data and meant experiments had to be repeated.
“Now, we’re saying there is evidence of strain structure, so now we have to revise the theory,” Day said. “But we have to inform that theory with experiments.”
Her theory suggests that the malaria parasite is less transmissible than previously thought. Rather than an infection in one person causing potentially dozens of infections in others, secondary cases may typically number only five or six, she said. This suggests malaria isn’t as difficult a foe to control as previously thought.
Day’s current work involves studying the effects of bed nets and other control tools on the persistence of malaria and new strain evolution among 2,000 people in a village in Ghana.