Malaria vaccine achieves striking early success

doi:10.1126/science.372.6541.448

GSTDTAP > 气候变化

DOI	10.1126/science.372.6541.448
	Malaria vaccine achieves striking early success
	Meredith Wadman
	2021-04-30
发表期刊	Science
出版年	2021
英文摘要	After decades of disappointing results, new findings have revived hopes for an effective vaccine against malaria, which kills some 400,000 people every year, most of them children. An experimental vaccine that targets the most dangerous form of the malaria parasite was found to have an efficacy of 71% to 77% after 1 year in children. The results, posted as a preprint last week, come from a trial of a vaccine developed by researchers at the University of Oxford's Jenner Institute involving 450 toddlers in Burkina Faso, where malaria is endemic. “The efficacy we have got has never been obtained by any [malaria] vaccine candidate. These are really amazing findings,” says trial site co–principal investigator Halidou Tinto, a parasitologist at the Institute for Health Sciences Research in Nanoro, Burkina Faso. The results are “very positive news,” says Pedro Alonso, director of the World Health Organization (WHO) Global Malaria Programme, who was not involved with the work. But he and others note the trial's small size and that the vaccine's protection was really only demonstrated during the 6 months when malaria was most prevalent in Burkina Faso; scarcely any malaria cases occurred at other times. “We are still quite far away from having the type of information that would allow us to get very excited,” he says. But the new study's investigators are bullish and plan to launch a pivotal phase 3 trial later this year, enrolling 4800 children in Burkina Faso, Mali, Kenya, and Tanzania. In the best case, data from that trial could be submitted to regulators late in 2022 for approval in early 2023, says Oxford's Adrian Hill, the trial's chief investigator. He hopes that the phase 3 results will persuade regulators to issue emergency use authorizations, as they have for COVID-19 vaccines. The children in the current trial, aged 5 months to 17 months, received three doses of vaccine at 4-week intervals and a booster at 12 months. Of the 146 children whose vaccine included a high dose of an immune-boosting compound called an adjuvant, 39 developed malaria, versus 106 of 147 children in a control group who received rabies vaccine. (The rabies shots ensured the control group also received value from being in the trial.) The 77% efficacy against malaria dipped to 71% in children who got a vaccine with a lower dose of adjuvant. The children's levels of specific antibodies to malaria fell by two-thirds by 9 months, but the booster dose at 12 months restored them, according to the paper, which is in press at The Lancet and was posted 20 April on its preprint server. WHO has called for the development of vaccines that can reduce malaria cases by 75% by 2030. But the malaria parasite's complex life cycle and shifting surface proteins have challenged vaccine developers. The highest efficacy previously published for a vaccine at 1 year after dosing was 56%, for Mosquirix, made by GlaxoSmithKline (GSK), Hill notes. Mosquirix's efficacy in a large trial dropped to 36% after about 4 years, and some scientists worry the same could happen with the Oxford vaccine: The vaccines are structurally similar and both target the parasite right after infection. Hill believes his team's vaccine will have staying power. The Oxford vaccine consists of hepatitis B protein combined with part of a protein that coats the surface of the malaria parasite. The hepatitis B proteins self-assemble into a “viruslike particle” densely studded with malaria proteins—more densely than in GSK's vaccine. Hill thinks this amplifies antibody responses and protection. The Serum Institute of India is making the Oxford vaccine for a planned phase 3 trial and has pledged to produce 200 million doses in the coming years. “The price [will be] less per dose than ever before,” Hill says. The potent adjuvant, a purified plant compound called a saponin, made by Novavax, is already being manufactured at scale for that company's COVID-19 vaccine. Others caution that many unknowns remain. In many countries, malaria transmission is continuous, not seasonal, notes Robert Sauerwein, a medical microbiologist at TropIQ Health Sciences in Nijmegen, Netherlands. “The real issue, sustained protection and induction of sustained [immunological] memory, has not been addressed yet,” he says. (The investigators are currently following the children in the trial out to 24 months.) Others called out what they saw as deficiencies in the study. “Where's the biology?” asked Rhoel Dinglasan, who is developing another malaria vaccine at the University of Florida's Emerging Pathogens Institute. He applauded the new results, but wanted to see genomic data on the malaria parasites that managed to infect vaccinated children. Dinglasan says that without sequence data, it's not clear whether the vaccine will be effective against all parasite strains. The efficacy of the GSK malaria vaccine fell by one-third, to 33.4%, when there was a mismatch between a key part of the protein used in the vaccine and the corresponding protein in the parasite, he notes. And a mismatched vaccine could drive selection for vaccine-resistant parasites, potentially thwarting the quest for a highly effective vaccine once again.
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/325010
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Meredith Wadman. Malaria vaccine achieves striking early success[J]. Science,2021.
APA	Meredith Wadman.(2021).Malaria vaccine achieves striking early success.Science.
MLA	Meredith Wadman."Malaria vaccine achieves striking early success".Science (2021).