Exposure to Late Stages of Malaria May Inhibit Immunity to Early Stages of Infection

Researchers discover that being exposed to latter stages of malaria infection prevents cells from developing immunity to early liver stage infection.

Researchers from the University of Washington School of Medicine recently published a study on malaria vaccine response in the journal, Cell Reports. They found that some individuals living in malaria-endemic regions are exposed to a “blood stage,” or late stage, of malaria that inhibits immunity to the “liver stage,” or early stage, of the infection.

The World Health Organization reports that between 2010 and 2015, more than 200 million individuals were newly-diagnosed with malaria, with 90% of cases in the African region; this is a 21% drop from previous years. Approximately 430,000 individuals around the world lost their lives to this disease in 2015, with the highest number of casualties also being in the African region. About 300,000 of those who died due to a malaria infection were under 5 years of age. In addition, according to recent studies, malaria has been traveling fast to nonendemic areas, with more than 4,000 imported cases in France and the United Kingdom alone.

To successfully prevent infection with the mosquito-borne disease, a vaccine that tackles both early and late stages of malaria is needed, according to Marion Pepper, PhD, researcher and assistant professor of immunology at the University of Washington School of Medicine. Dr. Pepper and her colleagues conducted lab studies in mice to see how the blood stage of the disease suppresses immunity to the liver stage.

In a press release, Dr. Pepper commented on her team’s research, saying, “Malaria has evolved with us throughout human existence and therefore has some potent immune evasion strategies. We really tried to tease apart some of the factors that could be driving the loss of protective immunity during natural infection and with current vaccine strategies in areas of high malaria transmission.”

The mice, which were split up into two groups, were infected with two forms of the malaria parasite; one of which was modified so that it would not develop past the liver infection stage, while the other was able to develop to the blood-stage infection. After 6 days of initial infection, the researchers observed that mice that were infected with liver-stage­—modified malaria had significantly higher antibody levels than those that went on to develop a blood-stage infection.

Trying to decipher why this may be, the research group studied Plasmodium liver stage-specific B cells that are able to separate to become either “antibody-secreting early effector cells or long-lived memory cells, both of which contribute to protection against malaria,” according to the press release. After 14 days of infection, the researchers observed that, in mice infected with blood-stage malaria, the B cells “never went through the necessary changes to make rapidly responsive memory cells.” Nonetheless, B cells in the mice of the other group “were still able to differentiate and create the necessary antibodies and memory cells for an effective immune response.” The researchers also found that, when treated, B cells of those with liver-stage malaria were able to function properly and develop the “optimally responsive memory cells.”

The next stage of Dr. Pepper’s research will focus on finding a cure for the discrepancy between those patients in whom malaria progresses into a blood-stage infection.

According to Dr. Pepper, “This work really highlights the importance of looking at antigen-specific B cells. These data also suggest that if you’re getting a vaccine while you have an ongoing blood stage infection, there is a chance that the vaccine will not generate good memory cells because the blood stage disrupts all the processes that are involved in making that immunological memory.”