In the past, it was widely assumed that our poor ability to fight malaria infection was due to the malaria parasite’s ability to evade immune detection. However, research published today in Cell Reports suggests that there is more to the story. In fact, our bodies actually do create potent antibodies in response to malaria infection.
“It is well known that an individual must continuously be exposed to malaria over many decades in order to develop protective immunity, during which time they are often sick, as well as spreading the disease,” says senior author Diana Hansen of the University of Melbourne. “We wanted to know what makes malaria infection different to so many other diseases, where a single exposure confers immunity for life.”
In the case of malaria, the researchers found that inflammatory signals actually improved antibody quality. The immune system was not previously known to produce such potent antibodies to malaria infection. So the question was, why does immunity against malaria require decades of exposure?
“What we determined was that inflammatory signals simultaneously improve the quality of the antibody response while limiting its magnitude,” Hansen says. “So the B cells, even though they are of elite quality, are not able to have as much impact on future infections.”
According to Hansen, this new discovery could have a role beyond malaria. “I think this discovery is so exciting because of the opportunity it offers in treating chronic viral infections and autoimmune disease,” she says. “We have identified the molecular ‘switch’ that drives the immune system to produce highly potent antibodies, and the inflammatory signals that influence its function. Targeting this molecule, or other molecules in the same pathway, could offer a more ‘precision medicine’ approach to treating these diseases than currently exists.”
In chronic infections—including malaria, HIV, and hepatitis C—producing potent, high-quality antibodies is critical for clearing the infection. On the flip side, B cells that are primed to make antibodies that target self-antigens—our body’s own proteins and tissues—are incredibly destructive, leading to autoimmune diseases such as lupus.
“The hope is that we would be able to create vaccines or therapies that would ‘switch on’ molecules that help to produce these elite B cells to fight chronic infections better, or ‘switch off’ the same molecules in autoimmune diseases to stop the production of B cells, such as in lupus,” Hansen says.
Image: In this image, we see B cells (green) producing antibody (brown). Image courtesy of Walter and Eliza Hall Institute.