Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus.

Autor:	Ren Z; State Key Laboratory of Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Li M; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Chen J; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Gong X; Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People's Republic of China., Song S; Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People's Republic of China., Li D; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, People's Republic of China., Yang M; School of Life Science, Advanced Research Institute of Multidisciplinary Science, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, People's Republic of China., Yu J; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Asghar S; Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan., Cui Y; Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People's Republic of China., Niu S; Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People's Republic of China., Liao Z; Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People's Republic of China., Jiang Y; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Liu J; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Li Y; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Zhang B; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Zhao W; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Peng J; State Key Laboratory of Organ Failure Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China., Yang Y; Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, People's Republic of China., Shen C; BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health; Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.; Key Laboratory of Infectious Diseases Research in South China, Southern Medical University, Ministry of Education, People's Republic of China.
Jazyk:	angličtina
Zdroj:	Emerging microbes & infections [Emerg Microbes Infect] 2024 Dec; Vol. 13 (1), pp. 2401931. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1080/22221751.2024.2401931
Abstrakt:	In 2022, the monkeypox virus (mpox virus, MPXV) exhibited global dissemination across six continents, representing a notable challenge owing to the scarcity of targeted antiviral interventions. Passive immunotherapy, such as the use of monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), has emerged as a promising option for antiviral regimens. Here, we generated several mAbs against M1R and B6R of MPXV, and subsequently characterized the antiviral activity of these antibodies both in vitro and in vivo . Two neutralizing mAbs, M1H11 and M3B2, targeting M1R, and one B6R-specific mAb, B7C9, were identified. They exhibited varying antiviral efficacy against vaccinia virus (VACV) in vitro and in vivo . A cocktail comprising M1H11 and M3B2 demonstrated a superior protective effect in vivo . A bsAb, Bis-M1M3, was engineered by conjugating the fragment crystallizable (Fc) region of the human-mouse chimeric engineered M1H11 with the single-chain fragment variable (scFv) of M3B2. In mice challenged with MPXV, Bis-M1M3 showed a notable protective effects. Analysis of neutralization mechanism showed that these mAbs and Bis-M1M3 exerted virus-neutralizing effects before the virus infects cells. In vivo pharmacokinetic experiments showed that Bis-M1M3 has a long half-life in rhesus macaques. This study provides crucial insights for further research on broad-spectrum antiviral drugs against MPXV and other orthopoxviruses.
Databáze:	MEDLINE
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