Researchers move closer to Malaria vaccine that could finally stop disease that kills nearly half a million every year
A multi-university research project, led by the University of Oxford, has identified the human antibodies that prevent the malaria parasite from entering blood cells, which could hold the key to creating the first effective vaccine against malaria infection in the blood.
“We next need to design novel vaccine components which cause the human immune system to generate only the most effective and most protective antibodies. Developing vaccines against a challenging pathogen like malaria is a slow process. But we are already testing a vaccine component designed to specifically cause one of the most protective antibodies to be induced,” study co-author Matthew Higgins from the Department of Biochemistry at the University of Oxford, told MEA WorldWide (MEAWW).
According to the World Health Organization (WHO) estimates, while there were 219 million malaria cases worldwide in 2017, it was responsible for 435,000 deaths globally the same year.
Study author Simon Draper, Professor of Vaccinology and Translational Medicine at the Nuffield Department of Medicine, University of Oxford, explained that following an infectious mosquito bite, the malaria parasite first goes in the human liver and subsequently moves into the blood, where it replicates 10-fold in the blood cells every 48 hours.
It is this stage of the infection that leads to the illness and can be fatal. The research team further said that the malaria parasite has a protein called RH5, which must bind to a human protein on the red blood cells called basigin to infect them.
In this study, published in the journal Cell, the researchers were able to demonstrate which human antibodies effectively block RH5 from binding with basigin, thus preventing the parasite from spreading through the blood.
“Malaria parasites have to be able to get inside red blood cells to divide, and if we can prevent this ‘invasion’ process, we can stop malaria. The RH5 molecule is used by the parasite to allow it to invade blood cells. We immunized volunteers in Oxford with a vaccine which contains the RH5 molecule and identified the antibodies that these volunteers produced in response to vaccination. We discovered which antibodies were most able to prevent the parasite from getting inside the blood cells,” Dr. Higgins said.
He added, “The parasite has to get inside blood cells to spread within the blood, and the antibodies stop this process. If it cannot get inside blood cells, the parasite cannot replicate, and it is trapped outside the cells, where the human immune system can detect it and destroy it.”
Another key finding of the study is the identification of an exciting new antibody, which works by slowing down the speed in which RH5 binds to red blood cells.
“The work has given us the first insight into the most effective ways for our immune system to attack a weak point in the malaria parasite. An exciting and surprising finding to come out of this work is that a very specific type of antibody slows the invasion of malaria into red blood cells, giving the immune system more time to kill the malaria parasite. This finding will allow us to design new vaccines which leverage this slowing effect for the first time by teaching the immune system to make this special type of antibody. The implications are that we previously thought our immune system was limited to attacking the blood-borne form of malaria for a very short time window, but these new data show us that this time window to attack can be extended,” researcher and co-author of the study Dr. Daniel Alanine, told MEAWW.
Dr. Higgins said normally, people in a vaccine design strategy aim to find out what the protective antibodies are and work out how to get the vaccinated individual to produce these antibodies.
“In this case, we found a non-protective antibody, which could make the protective antibodies better. It does this by slowing down the process of invasion, meaning that the parasite takes longer to get inside the red blood cells,” he said.
The study was done as part of a clinical trial in Oxford of the first vaccine that targets the RH5 malaria protein. Until now, however, it was not clearly understood which specific antibodies could be generated by vaccination of a human volunteer and would effectively prevent RH5 from binding to red blood cells.
Dr. Higgins said that the Draper lab published the first demonstration that RH5 was a good vaccine candidate in 2011, and it has been about nine years since the team started to work on this.
“Since then, we have shown that RH5 vaccination is protective in an animal model of malaria, worked out how RH5 binds to its receptor on blood cells, and have conducted these clinical trials. Future studies will use structure-guided methods to design better vaccines,” he added.
When someone is vaccinated, they make many different types of antibodies against the same RH5 target. The research team said that the key to stopping malaria is a strong immune response, and so every antibody counts.
“What we must do next is use these findings to develop an improved RH5 vaccine that induces more of the effective antibodies and less of the non-effective ones. This will ultimately make a better vaccine, and hopefully lead to an effective means of preventing malaria,” said Dr. Draper.