“Landmark” research found that artificial antibodies can protect against malaria | Chemistry

Add malaria to the list of infections that Lab antibodies may one day prevent. In a rare study, nine people who received these monoclonal antibodies were deliberately exposed to mosquitoes that carry the parasites that cause malaria. No one was infected and protection seems to last for more than half a year.

This test is too small to reach a firm conclusion about the efficacy of monoclonal antibodies and is not a real test, but people in this field are trying to prove the principle to pave the way for the prevention of fatal diseases. I’m impressed. “That’s great,” said Dennis Burton, an immunologist at Scripps Research, who developed the monoclonal antibodies COVID-19, and Zika to prevent HIV infection. “This is a groundbreaking study.”

Monoclonal antibodies are expensive to manufacture and may be out of reach of many developing countries, but this work may also help in efforts to develop better malaria vaccines than those currently in widespread use. there is.It demonstrates the importance of targeting the immune response to important regions of the protein produced by the spore-like stage. Plasmodium falciparum, Protozoa that are responsible for most of the malaria deaths in the world. Prophylactic antibodies bind to a small portion of these sporozoite surface-studded peri-sporozoite proteins (CSPs). “This is the first study to actually evaluate the efficacy of antibodies against human CSP targets,” said Hedda Wardemann, an immunologist studying anti-malaria antibodies at the German Cancer Research Center.

There are already medicines that can temporarily protect people Plasmodium falciparum— Many travelers to areas suffering from malaria take them. The drug is also used by some populations living in areas with malaria seasons. The malaria season is usually associated with rain and mosquito population explosions. Also, mosquito nets and pesticides can make it more difficult for mosquitoes to eat our blood and become infected.But Plasmodium falciparum Still, at least 200 million people get sick each year and an estimated 400,000 die.

The research team first isolated the CSP antibody Plasmodium falciparum From a person who received an malaria vaccine. Parasites that fly between mosquitoes and humans have a complex multi-step life cycle, and antibodies prevent sporozoites from infecting liver cells. Liver cells mature into other forms that can destroy red blood cells and cause disease.

Plasmodium falciparum It is notorious for developing resistance to anti-malaria drugs and impairing the ability to prevent or treat the disease. Previous study analyzing the genetic composition of 6500 isolates Plasmodium falciparum It can be seen that 99.9% are identical in the region of CSP targeted by this antibody. The “highly conserved” nature of the CSP region means that the parasite needs it to survive, so researchers infer that it cannot be easily mutated in a way that avoids antibodies. Did.

A team led by immunologist Robert Seder of the National Institute of Allergy and Infectious Diseases Vaccine Research Center manipulated Chinese hamster ovary cells to mass-produce modified versions of antibodies that were more than twice as sustainable. .. In the body before it is broken down.In a empirical study, the team injected antibodies into people and allowed mosquitoes to carry them. Plasmodium falciparum To feed their arms. None of the people who received the antibody in this “challenge” trial could detect blood levels of the parasite., 5 out of 6 in the untreated control group, but the research team today New England Journal of Medicine.. (They were treated immediately and no one got sick.)

The COVID-19 pandemic interrupted the original plan of the study to give antibodies to participants and expose all participants to infected mosquitoes after a few weeks. The two had no parasite challenge for 36 weeks. Researchers have suggested that their successful protection may protect people for more than 6 months with a single injection of monoclonal antibody.

Seder envisions that travelers, military personnel, or healthcare professionals visiting the malaria area for extended periods of time will receive the monoclonal antibody. This is something that companies can mass produce. Ideally, the clinic will give a relatively low dose of antibody by subcutaneous injection. This is a much easier and cheaper option than the relatively high doses this study gave by injecting into the bloodstream.

More ambitious use of anti-malaria monoclonal antibodies will administer them in disease-bearing geographic areas. Antibodies may be especially useful for children and pregnant women at high risk of severe illness because they did not have time to develop innate immunity. Plasmodium falciparum infection.Cedar is a person who is repeatedly exposed Plasmodium falciparum It developed a complex immune response against parasites and endangered an malaria vaccine that worked well in clinical trials in unexposed people. “When I got this result, people said to me,’Have you ever broken champagne?'” Says Cedar. “I said,’No, I drank beer.’ I only serve champagne if I have data from Africa.”

In 2019, three African countries began extensive testing of an malaria vaccine called RTS, S, which uses different parts of CSP. As of April, the pilot program administered RTS, S four times to 650,000 infants. In previous clinical trials, RTS, S reduced the infection rate in fully immunized children by 50% after one year, but by the fourth year it had dropped to 28%. Wardemann hopes that large-scale studies with monoclonal antibodies like Seder will help vaccine researchers identify which parts of the CSP stimulate a more effective or long-term immune response. It states that it is.

W. Ripley Burrow, who worked on the International AIDS Vaccine Initiative and pioneered the development of RTS, S, states that producing monoclonal antibodies at the doses used in Cedar’s research would cost more than $ 100 for a 50-kilogram person. I have malaria. “This is a good proof of concept, but it’s not yet ready for intervention,” he says.

Cedar agrees. He is developing a new monoclonal antibody that is two to three times more potent, and his team plans to test it in a clinical trial in Mali next year. He also hopes that the next generation of monoclonal antibodies will be even more powerful. “I assume my antibody is more than 90% effective for 6 months with a single subcutaneous injection,” says Seder. “Is it a tool that a country can use to eradicate malaria?”

Wardemann says monoclonal antibodies may ultimately contribute to a multifaceted elimination strategy. “I don’t think antibodies alone can do that,” she says. “So far, we haven’t done that with a single measure.” Mosquito nets, drugs and vaccines have helped control malaria in several places. “The above antibodies may help,” she says.