دورية أكاديمية
Delayed treatment of cynomolgus macaques with a FVM04/CA45 monoclonal antibody cocktail provides complete protection against lethal Sudan virus infection.
| العنوان: | Delayed treatment of cynomolgus macaques with a FVM04/CA45 monoclonal antibody cocktail provides complete protection against lethal Sudan virus infection. |
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| المؤلفون: | Chan M; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Warner BM; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Audet J; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Barker D; Research and Development, Emergent BioSolutions Canada, Winnipeg, Manitoba, Canada., Tailor N; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Vendramelli R; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Truong T; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Tierney K; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Boese AS; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada., Qiu H; Research and Development, Emergent BioSolutions Canada, Winnipeg, Manitoba, Canada., Holtsberg FW; Integrated BioTherapeutics, Rockville, Maryland, USA., Aman J; Integrated BioTherapeutics, Rockville, Maryland, USA., Kodihalli S; Research and Development, Emergent BioSolutions Canada, Winnipeg, Manitoba, Canada., Kobasa D; Special Pathogens program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada. |
| المصدر: | Journal of virology [J Virol] 2024 Aug 20; Vol. 98 (8), pp. e0124223. Date of Electronic Publication: 2024 Jul 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Antibodies, Monoclonal*/therapeutic use , Antibodies, Monoclonal*/immunology , Antibodies, Monoclonal*/administration & dosage , Antibodies, Viral*/immunology , Antibodies, Viral*/therapeutic use , Ebolavirus*/immunology , Hemorrhagic Fever, Ebola*/prevention & control , Hemorrhagic Fever, Ebola*/immunology , Hemorrhagic Fever, Ebola*/drug therapy , Treatment Delay*, Animals ; Female ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/therapeutic use ; Disease Models, Animal ; Macaca fascicularis ; Male |
| مستخلص: | Sudan ebolavirus (SUDV) is a member of the genus Ebolavirus (Family Filoviridae ) and has caused sporadic outbreaks of Ebola disease (EBOD), or more specifically Sudan virus disease (SVD), with high mortality rates in Africa. Current vaccines and therapies that have been developed for filoviruses are almost all specific for Ebola virus (EBOV; of the species Zaire ebolavirus ), and there is a current lack of therapeutics specific for SUDV. The recent SUDV outbreak in Uganda, which was distributed across multiple districts, including Kampala, a densely populated urban center, highlights the critical need for the development of novel SUDV-specific or pan-Ebola virus therapeutics. Previous work has characterized two monoclonal antibodies, FVM04 and CA45, which have neutralization capabilities against both EBOV and SUDV and have shown protective efficacy in animal challenge studies. Here, we expand upon this work, showing that treatment with a monoclonal antibody cocktail consisting of FVM04 and CA45 provides full protection against lethal SUDV infection in cynomolgus macaques. Studies that evaluate outcomes at late time points after infection, once clinical signs of illness are apparent, are vital for assessing the therapeutic efficacy of antibody therapeutics. We have shown that when treatment is initiated as late as 5 days after infection, with a second dose given on day 8, that treated groups showed few clinical signs or morbidity, with complete survival. This work provides further evidence that FVM04 and CA45 have strong therapeutic potential against SUDV and their development as a pan-Ebola virus therapeutic should be pursued. Importance: There are currently no approved vaccines or therapeutics for Sudan virus, a filovirus which is highly related to Ebola virus and causes similar disease and outbreaks. In this study, a cocktail of two potent monoclonal antibodies that effectively neutralize Sudan virus was tested in a nonhuman primate model of Sudan virus disease. Treatment was highly effective, even when initiated as late as 5 days after infection, when clinical signs of infection were already evident. All treated animals showed complete recovery from infection, with little evidence of disease, while all animals that received a control treatment succumbed to infection within 8 days. The study further demonstrated the strong therapeutic potential of the antibody treatment and supported further development for use in Sudan virus outbreaks. Competing Interests: S.K., H.Q., and D.B. are employees of Emergent BioSolutions Canada, which developed Ebola antibody used in these studies in collaboration with Integrated Biotherapeutics. F.W.H. and J. Aman are employees of Integrated BioTherapeutics, Inc., who developed and manufactured Ebola virus antibodies. All other authors declare no competing interests. |
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| معلومات مُعتمدة: | Public Health Agency of Canada (PHAC) |
| فهرسة مساهمة: | Keywords: Sudan virus; filovirus; immunotherapy; monoclonal antibody; nonhuman primate |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Antibodies, Neutralizing) 0 (Antibodies, Viral) |
| تواريخ الأحداث: | Date Created: 20240716 Date Completed: 20240820 Latest Revision: 20240826 |
| رمز التحديث: | 20240827 |
| مُعرف محوري في PubMed: | PMC11334508 |
| DOI: | 10.1128/jvi.01242-23 |
| PMID: | 39012096 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
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| DOI: | 10.1128/jvi.01242-23 |