London School of Hygiene & Tropical Medicine

The researchers found Plasmodium knowlesi, a malaria parasite carried by macaque monkeys in Southeast Asia, relies on a single gene called NBPXa to invade human red blood cells.

The study, conducted by researchers at the London School of Hygiene & Tropical Medicine and the Francis Crick Institute in London, opens a new research route to develop a vaccine to protect people from the disease.

P. knowlesi can hop between monkeys and people if a mosquito bites an infected macaque and then a person. It is the only malaria parasite that can infect both humans and animals and the disease is as severe as that caused by the most dangerous of the human malaria parasites.

Recent deforestation and changing land use brings macaque monkeys infected with P. knowlesi into closer contact with people. In 2014, Malaysia recorded 2,500 cases of monkey malaria in people. This is almost eight in every ten incidences of malaria and reports of the disease are increasing across South East Asia.

The research team looked at the process of red blood cell invasion using samples of monkey malaria in the lab. They found that NBPXa is essential for the parasite to infect human blood cells. When they stopped the gene from working the parasite still infected monkey cells but could no longer get inside human cells - a process essential for the parasite to multiply and spread.

The team collaborated with researchers in Saudi Arabia and Malaysia to generate a complete picture of the parasite's genetic code. They say a vaccine to protect against malaria caused by P. knowlesi is still a long way off.

Lead author Dr Rob Moon, from the London School of Hygiene & Tropical Medicine, said: "This is the first time a role for the NBPXa gene has been demonstrated in malaria, and it is a crucial one, allowing this potentially killer disease to invade human cells. Whether our research can be taken forward to develop a vaccine depends on how well antibodies against the NBPXa protein block parasite invasion of blood cells. We also know there is lots of variation in this protein in parasites strains from the field, so a vaccine will need to work against all strains - not just the ones in the lab."

Scientists have been working on a vaccine to protect against malaria caused by the human parasite Plasmodium falciparum. It is proving difficult because P. falciparum can use many different proteins to invade red blood cells. P. knowlesi doesn't have this flexibility as it uses just one protein to infect human cells. The team hope this lack of back-up infection options could make P. knowlesi much more vulnerable to a vaccine targeted at the blood cell infection stage in people.

Research team leader Dr Tony Holder from the Francis Crick Institute in London said: "The parasite's presence in wild monkeys means that controlling and eventually eradicating malaria caused by P. knowlesi will be extremely difficult. However, our study has found a weak link that could be exploited to develop a human vaccine to prevent this emerging disease."

Publication:

• Robert W. Moon, Hazem Sharaf, Claire H. Hastings, Yung Shwen Ho, Mridul B. Nair, Zineb Rchiad, Ellen Knuepfer, Abhinay Ramaprasad, Franziska Mohring, Amirah Amir, Noor A. Yusuf, Joanna Hall, Neil Almond, Yee Ling Lau, Arnab Pain, Michael J. Blackman and Anthony A. Holder. Normocyte binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi. Proceedings of the National Academy of Sciences. DOI:10.1073/pnas.1522469113