Blood from a rare group of children immune to malaria

Blood from a rare group of children from Tanzania, found to be naturally immune to malaria has now helped scientists take a giant leap in developing a vaccine against the world's deadliest vector borne disease — malaria.

Researchers from the Brown University School of Medicine have found that these children produce an antibody that attacks the malaria-causing parasite. Antibody is an infection-fighting protein produced by our immune system when it detects harmful substances.

Injecting a form of this antibody into mice protected the animals from the disease. Scientists say these antibodies would ultimately reveal the Achilles heel of malaria and help create the elusive vaccine.

This same principle has been used over the years in the work to create the world's first HIV vaccine. Globally, scientists have been trying to identify volunteers belonging to a rare group of HIV infected patients who stay healthy for years without requiring life-saving antiretroviral treatment (ART). The antibodies in their blood has been found to bar HIV from entering their blood cells and replicating, thereby progressing into AIDS.

Prof Jake Kurtis from the University screened 1,000 children in Tanzania, who had regular blood samples taken in the first years of their lives. Around 6% of these children were found to have developed a naturally acquired immunity to malaria, despite living in an area where the disease was highly active.

Scientists then looked into their blood and found a unique antibody that dealt a deadly blow to the malaria parasite at a key stage in its life-cycle. It trapped the tiny organism in red blood cells, preventing it from bursting out and spreading throughout the body.

Prof Kurtis said, "We asked what were the specific antibodies expressed by resistant children that were not expressed by susceptible children. Tests, carried out in small groups of mice, suggest this antibody could act as a potential vaccine. The survival rate was over two-fold longer if the mice were vaccinated compared to unvaccinated - and the parasitemia (the number of parasites in the blood) were up to four-fold lower in the vaccinated mice". Dr Kurtis and Dipak Raj of Brown University and Rhode Island Hospital have named their antibody PfSEA-1.

Dr Kurtis said, "PfSEA-1 was discovered by starting with naturally occurring protective human immune responses. Using molecular gymnastics, we identified parasite proteins that are only recognized by antibodies in children who were resistant to malaria but not by antibodies in susceptible children. We subsequently demonstrated that vaccination with one of these proteins, SEA-1 could protect mice from a lethal malaria infection. More importantly, in our cohort of over 750 children, kids who made antibodies to PfSEA-1 did not develop severe malaria, while children without these antibodies were susceptible to this severe complication".

"PfSEA-1 is essential to allow the parasite to escape from one infected red blood cell and infect additional blood cells. This cycle of expansion in red blood cells is critical for parasite survival and is the key process that leads to morbidity and mortality in humans. Using molecular techniques, we decreased the amount of PfSEA-1 that parasites could produce and demonstrated that these altered parasites had a significant growth defect. More importantly, antibodies to PfSEAs prevent the parasites from escaping from red blood cells, presumably by interfering with the function of PfSEA-1."

According to Dr Kurtis, there are three major areas for further study. "First, we need to understand the role that PfSEA-1 plays in the process of parasite egress from red blood cells. Cellular immunity is critical for long-lived antibody responses, but detailed analysis of cellular responses requires fresh blood samples, thus we are currently planning to enroll new cohorts in east Africa to address this question. We also need to move PfSEA-1-based vaccines into nonhuman primate challenge trials using human-use approved vaccine adjuvants. Following successful nonhuman primate studies, Phase I safety trials in humans can begin," he said.

The most recent figures from the World Health Organization suggest the disease killed more than 600,000 people in 2012, with 90% of these deaths occurring in sub-Saharan Africa.