Antibody acts like short-term malaria vaccine

doi:10.1126/science.373.6557.843

GSTDTAP > 气候变化

DOI	10.1126/science.373.6557.843
	Antibody acts like short-term malaria vaccine
	Jon Cohen
	2021-08-20
发表期刊	Science
出版年	2021
英文摘要	A powerful new weapon could one day join the global fight against malaria. Drugs and bed nets can already help protect against the disease, which still sickens at least 200 million people a year and kills an estimated 400,000. Vaccines have also shown some promise. But an unusual study reported last week dramatized the potential of monoclonal antibodies, made by genetically engineered cells. Nine volunteers who received the antibodies were deliberately exposed to mosquitoes carrying the parasite that causes malaria. None became infected—and the protection from the antibodies appears to last for more than 6 months. The trial is too small to reach firm conclusions about the monoclonals’ protective efficacy, but other researchers say it is a striking proof of principle. “It’s great,” says Dennis Burton, an immunologist at Scripps Research who has developed monoclonal antibodies to prevent HIV infection, COVID-19, and Zika. “This is a landmark study.” Monoclonal antibodies are costly to make, which could put them out of reach of many developing countries, but the work also informs efforts to improve malaria vaccines. It demonstrates the importance of targeting immune responses to the sporelike stage of Plasmodium falciparum , the protozoan responsible for most of the world’s malaria deaths. The preventive antibody binds to a small portion of the circumsporozoite protein (CSP) that studs the surface of these sporozoites. “It’s the first study that actually assesses the potency of an antibody against the CSP target in humans,” says Hedda Wardemann, an immunologist at the German Cancer Research Center. Several years ago, a research team first isolated a powerful CSP antibody from a person who received an experimental malaria vaccine. Previous studies that have analyzed the genetic makeup of thousands of isolates of P. falciparum showed that 99.9% are identical in the region of the CSP this antibody targets. The “highly conserved” nature of the CSP region means the parasite needs it to survive and thus, the researchers reasoned, it cannot easily mutate in a way that avoids the antibody. The team, led by immunologist Robert Seder of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, then engineered Chinese hamster ovary cells to churn out mass quantities of a version of the antibody modified to make it last longer in the body. The hope was the antibody would block a key step in the parasite’s complex life cycle, in which sporozoites infect human liver cells. There the parasite matures before emerging to destroy red blood cells and cause disease. In a “challenge” trial, the team gave infusions of the antibody to volunteers and then allowed mosquitoes carrying P. falciparum to feed on their arms. None developed detectable blood levels of the parasite, whereas five of six people in an untreated control group did, the research team reported in The New England Journal of Medicine . (The five promptly received treatment, and none became sick.) The group did not challenge two of the treated participants for 36 weeks because the pandemic delayed the research. They, too, were protected, which the investigators say suggests a single monoclonal antibody infusion could shield people for more than 6 months. Seder envisions that travelers, people in the military, or health care workers visiting malarial regions for prolonged periods might one day receive a single treatment with monoclonal antibodies before leaving home. This would be far simpler than taking daily antimalarial pills, which often have significant side effects and can also fail against resistant strains of P. falciparum . First, though, Seder says the monoclonals need to be tested in the real world. “People said to me when I got this result, ‘Have you broken out the champagne?’” he recounts. “I said, ‘No, I got a beer.’ I’ll only break out the champagne when I have data from Africa.” In the meantime, vaccine developers could benefit. An experimental malaria vaccine called RTS,S, which uses different parts of CSP to stimulate an immune response, had modest success in early clinical trials. Four doses cut infection rates in children by 50% after 1 year, but that dropped to 28% by year four. Although RTS,S has yet to receive regulatory approval, three African countries are part of a pilot program that has given the shots to more than 600,000 children. Wardemann says future studies with monoclonals like Seder’s could help vaccine researchers identify parts of the CSP that stimulate an even more effective or longer lasting immune response. Seder hopes monoclonals could one day supplement vaccines in regions that have a high burden of the disease. The antibodies might prove especially helpful to children, as they have not had time to develop much natural immunity, and to pregnant women, who are at increased risk of severe disease from a P. falciparum infection. But W. Ripley Ballou, who works at the International AIDS Vaccine Initiative and pioneered development of RTS,S, notes that manufacturing monoclonals at the doses used in Seder’s study would cost more than $100 for a 50-kilogram person—too expensive for most countries that have malaria. “This is a great proof of concept, but it’s not yet ready as an intervention,” he says. Seder agrees. His team is developing a more potent monoclonal antibody, which it plans to test next year in a clinical trial in Mali, and he anticipates further improvement. “Suppose my antibody is 90-plus percent effective for 6 months with one subcutaneous shot,” Seder says. “Is that a tool a country could use for elimination of malaria?” Maybe, Wardemann says, if added to bed nets, drugs, and vaccines. “No single measure has done it so far,” she says. “An antibody on top may help.”
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推荐引用方式 GB/T 7714	Jon Cohen. Antibody acts like short-term malaria vaccine[J]. Science,2021.
APA	Jon Cohen.(2021).Antibody acts like short-term malaria vaccine.Science.
MLA	Jon Cohen."Antibody acts like short-term malaria vaccine".Science (2021).