DSM-265

在一项新的研究中，研究人员成功地在体外---在不需要蚊子的培养皿中---制造传染性PfSPZ，在实现了生产规模的扩大以便最终满足了数亿至数十亿人的疟疾接种需求方面迈出了关键的第一步。 Sanaria公司开发的恶性疟原虫（Plasmodium falciparum）子孢子（PfSPZ）疫苗在无需加强注射任何疟疾疫苗的情况下对恶性疟原虫感染具有最高的保护效力，而且保护效力持续时间最长。PfSPZ疫苗是在符合国际监管标准的条件下在蚊子体内制造的。 在一项新的研究中，来自美国Sanaria公司等研究机构的研究人员成功地在体外---在不需要蚊子的培养皿中---制造传染性PfSPZ，在实现了生产规模的扩大以便最终满足了数亿至数十亿人的疟疾接种需求方面迈出了关键的第一步。相关研究结果于2022年12月7日在线发表在Nature期刊上，论文标题为“In vitro production of infectious Plasmodium falciparum sporozoites”。 培养疟原虫的血液阶段（导致疾病并传播给蚊子）的能力对我们加深对寄生虫生物学的理解具有巨大影响，并为疫苗开发提供了重要工具。 西班牙巴塞罗那大学全球健康教授Pedro Alonso博士说，“在体外常规生产PfSPZ的能力同样会引发变革，因为它将加快我们审视疟原虫这一鲜为人知的血液阶段的生物学特性的能力，该阶段通常通过受感染蚊子的叮咬传播给人们。” 这篇论文首次描述了在不需要蚊子的情况下完成恶性疟原虫的生命周期，并通过基因表达、抗原表达、形态学和感染性研究在细胞、分子和功能水平上描述了体外PfSPZ与蚊子产生的PfSPZ的比较生物学特征。 体外的疟原虫动合子和卵囊。图片来自Nature, 2022, doi:10.1038/s41586-022-05466-7。 美国西雅图儿童研究所高级副总裁兼首席研究运营官Eric Tham博士补充说，“我们为全球传染病研究中心的Stefan Kappe博士领导的疟疾疫苗研究团队对这项开创性研究的贡献感到自豪，并期待着与Sanaria公司未来在这项技术的基础上开展合作，以生产高保护性的基因减毒PfSPZ疫苗。” Sanaria公司的使命一直是开发、生产、许可和部署具有高度保护性的PfSPZ疫苗，作为控制和最终消除这种寄生虫病的工具。这种疾病每年造成60多万人死亡，其中大部分是非洲儿童，对非洲大陆的孕妇造成不同程度的不利影响，并造成难以计数的住院人数、因病损失的天数以及数十亿美元的控制和治疗费用。 瑞士艺术与科学院院长Marcel Tanner教授强调了这篇论文的重要性，他说，“这篇关键论文中提出的方法为Sanaria公司真正解决这一未满足的需求铺平了道路，该方法不仅可以在规模上扩展，而且可以随时转让给世界上任何想要生产PfSPZ疫苗的国家。”（生物谷 Bioon.com） 参考资料： Abraham G. Eappen et al. In vitro production of infectious Plasmodium falciparum sporozoites. Nature, 2022, doi:10.1038/s41586-022-05466-7.

Scientists report a new way to test vaccines that may be as rigorous and stringent as exposure to field strains of malaria. Malaria is the deadliest mosquito-borne parasitic infection of humans. In 2021, after a century of research, the World Health Organization (WHO) approved the world's first malaria vaccine. That vaccine reduces the incidence of malaria infections in young children aged 5-17 months by only 30 percent, meaning that it remains critical to continue developing and testing more effective vaccines. WHO's goal is to find a vaccine that prevents infection as well as cases of severe malaria. However, testing vaccines in the field is challenging and requires large number of volunteers and long periods of follow-up. This process increases the expense and reduces the number of trials that researchers can perform. Now, scientists at the University of Maryland School of Medicine's (UMSOM) Institute for Genome Sciences (IGS) and the UMSOM Center for Vaccine Development and Global Health (CVD), and their collaborators report a new way to test vaccines that may be as rigorous and stringent as exposure to field strains of malaria. Their study was published in the June issue of Nature Communications. Their method has two key aspects. First, they expose vaccinated volunteers to malaria in a controlled clinical environment. Secondly, for this testing, they use a strain of malaria that is genetically very different from the one used in the vaccine, as well as from strains in the geographic region to which the vaccine is intended. This technique allows scientists to test how well the vaccine works in small numbers of volunteers under controlled settings and in a rapid fashion and predicts how well the vaccine may perform in the field. This lets researchers select the best vaccines for larger studies in the field. This method will increase the efficiency of vaccine testing and should accelerate malaria vaccine development. "The standard for many investigators has been to test vaccines with a strain similar to the one used in the vaccine's development," explained the study's lead author, Joana Carneiro da Silva, PhD, Professor of Microbiology and Immunology at UMSOM and IGS. "Using a strain that is both genetically distant from the one in the vaccine -- as well as from the strains circulating in the area where malaria is rampant and the vaccine will be used- is a more stringent way to test vaccine effectiveness." Researchers are studying the effectiveness of a vaccine (PfSPZ Vaccine) made by the company Sanaria, Inc, based in Rockville, Maryland. This vaccine uses the West African parasite strain known as PfNF54. One objective is to use this vaccine to protect individuals with little or no previous exposure to malaria, including those living or traveling in Africa. The long-term goal is to use the vaccine in mass vaccination programs to eliminate malaria from specific regions in Africa. For the study, researchers infected mosquitoes with a Brazilian malarial strain and then exposed U.S. volunteers who had been vaccinated with the Sanaria vaccine (as well as those who received a placebo) to the bites of infected mosquitos in a controlled clinical setting. They also vaccinated research participants in Mali with the same dose of the vaccine to compare observed vaccine efficacy in the field with that in the clinic. Through genomic sequencing, researchers had shown that the Brazilian strain differed greatly from 700 strains previously collected from across Africa, including the one used to make the vaccine. The researchers looked at about 200 volunteers in four trials -- two in the United States and two in Mali. In all four, they observed how many people became infected with malaria, as well as how long it took for them to become infected, comparing clinic to field. At the end of six months, they found the vaccine was just as effective in both populations. In addition, previous comparisons had shown that those volunteers who had never been exposed to malaria developed more antibodies than those in the field, proving that it would work well in first-time travelers to the area. The research team included scientists from Sanaria Inc.; the Naval Medical Research Center; University of Tübingen in Germany; the Malaria Research and Training Center in Bamako, Mali; and the Laboratory of Malaria Immunology and Vaccinology at NIAID, NIH. The World Health Organization estimates that in 2020, 241 million cases and 627,000 deaths worldwide were due to malaria, including 2,000 cases diagnosed in the United States from travelers and immigrants who were exposed elsewhere. The variety of malarial strains globally makes vaccine development particularly difficult. "Given the diversity of malaria strains worldwide, this research demonstrates that the Brazilian strain is as diverse as any strain detected in Africa," said Kirsten E. Lyke, MD, Professor of Medicine and Director of the Malaria Vaccine and Challenge Unit at the CVD and an author of the paper. Dr. da Silva noted this new model can be used in the future in selecting challenge strains to test the efficacy of vaccines against other parasitic diseases, using carefully controlled clinical settings to compare against field studies. This study was funded the National Institutes of Health's National Institute of Allergy and Infectious Diseases intramural program and grants (U19AI110820, R01AI141900, 5R44AI058375-10, and 5R44AI055229-11) , and the Department of Defense (W81XWH1420011).