Many efforts to develop malaria vaccines in recent decades have focused on triggering an immune response to prevent the disease from infecting liver cells. But researchers at the Burnet Institute have examined the potential to attack the parasite earlier – as soon as it enters the bloodstream from a mosquito bite – and they've identified an important mechanism for vaccines to target.
The reason the liver has been such a focus for malaria researchers is because the parasites migrate to this organ to mature and reproduce, resulting in the massive infection of red blood cells. But Dr Gaoqian Feng, who led the study, points out that it can take a couple of hours after a mosquito bite for the parasites to get to the liver.
“It’s a bit like saying, we’re going to build a big wall, and we’ll let the invading troops come and we’ll knock them off at the wall – but that’s risky because if they find a way through, you’re finished."
In the hope of finding a way to deal with the infection before it takes hold in the liver, the researchers looked at various immune cells, searching for one with the ability to mount a defense and destroy pathogens or infectious organisms soon after someone is bitten.
Their search led them to neutrophils, which are an essential component of the immune system. They comprise from 40 to 70 percent of all white blood cells in humans and, although they don’t live long, they are highly mobile and able to enter parts of tissue that other cells and molecules can't, making them ideal first responders.
Despite this, the researchers say very little was known about the role they play in attacking malaria. Encouragingly, they found that the immune system is able to mount an early attack against the parasite when it is in the bloodstream, with neutrophils shouldering most of the load. Specifically, they are able to work in combination with antibodies, which coat the parasites before the neutrophils join the fight and deliver a knock-out blow.
"What this research has established for the first time is not just how neutrophils act, but their characteristics and an understanding of their molecular mechanisms,” says Professor Beeson, Head of Burnet's Malaria Immunity and Vaccines Laboratory. "Most importantly, what it’s yielded is proof of principle to inform how to go forward with a vaccine to maximize protection against malaria."
The researchers say the new knowledge opens up a couple of prospective paths for vaccine development, such as pursuing combination approaches that target the infection in the blood and the liver, or modifying existing vaccines, which currently only achieve efficacy rates of up to 36 percent in infants and young children.
The study, which also involved researchers from the University of Melbourne, Case Western Reserve University, Maseno University, and QIMR-Berghofer Institute, appears in the journal Nature Communications.
Source: Burnet Institute
