Wai Kwan Tang, Nichole D. Salinas, Surendra Kumar Kolli, Shulin Xu, Darya V. Urusova, Hirdesh Kumar, John R. Jimah, Pradeep Annamalai Subramani, Madison M. Ogbondah, Samantha J. Barnes, John H. Adams, Niraj H. Tolia
{"title":"多级保护性抗 CelTOS 单克隆抗体对疟疾具有跨物种无菌保护作用","authors":"Wai Kwan Tang, Nichole D. Salinas, Surendra Kumar Kolli, Shulin Xu, Darya V. Urusova, Hirdesh Kumar, John R. Jimah, Pradeep Annamalai Subramani, Madison M. Ogbondah, Samantha J. Barnes, John H. Adams, Niraj H. Tolia","doi":"10.1038/s41467-024-51701-2","DOIUrl":null,"url":null,"abstract":"<p>CelTOS is a malaria vaccine antigen that is conserved in <i>Plasmodium</i> and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either <i>P. falciparum</i> or <i>P. vivax</i> CelTOS, and with transmission reducing activity against <i>P. falciparum</i>. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat <i>P. falciparum</i> and <i>P. vivax</i> malaria.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":null,"pages":null},"PeriodicalIF":14.7000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria\",\"authors\":\"Wai Kwan Tang, Nichole D. Salinas, Surendra Kumar Kolli, Shulin Xu, Darya V. Urusova, Hirdesh Kumar, John R. Jimah, Pradeep Annamalai Subramani, Madison M. Ogbondah, Samantha J. Barnes, John H. Adams, Niraj H. Tolia\",\"doi\":\"10.1038/s41467-024-51701-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>CelTOS is a malaria vaccine antigen that is conserved in <i>Plasmodium</i> and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either <i>P. falciparum</i> or <i>P. vivax</i> CelTOS, and with transmission reducing activity against <i>P. falciparum</i>. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat <i>P. falciparum</i> and <i>P. vivax</i> malaria.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.7000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-024-51701-2\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-024-51701-2","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria
CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either P. falciparum or P. vivax CelTOS, and with transmission reducing activity against P. falciparum. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat P. falciparum and P. vivax malaria.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.