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

Ren, Zuning1,2,3; Li, Mengjun2,3; Chen, Jiayin2,3; Gong, Xiaohua4; Song, Shuo4; Li, Delin5; Yang, Minghui6; Yu, Jianhai2,3; Asghar, Sadia7; Cui, Yanxin4; Niu, Shiyu4; Liao, Zhonghui4; Jiang, Yushan2,3; Liu, Jiahui2,3; Li, Yuqing2,3; Zhang, Bao2,3; Zhao, Wei2,3; Peng, Jie1; Yang, Yang4; Shen, Chenguang2,3,8

2024-12-31

10.1080/22221751.2024.2401931

EMERGING MICROBES & INFECTIONS   影响因子和分区

2222-1751

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.

Mpox virus Vaccinia virus Monoclonal antibody Bispecific antibody Antiviral mechanism

SCI

英语

通讯

National Natural Science Foundation of China["32170939","82371846","32411540019"] ; Guangdong Basic and Applied Basic Research Foundation[2022B1515020075] ; Guangdong Science and Technology Program key projects[2021B1212030014] ; Special Funds for Strategic Emerging Industry of Shenzhen[F-2022-Z99-502266]

Immunology ; Infectious Diseases ; Microbiology

Immunology ; Infectious Diseases ; Microbiology

WOS:001316099600001

TAYLOR & FRANCIS LTD

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Infect Dis, State Key Lab Organ Failure Res, Guangzhou, Peoples R China
2.Southern Med Univ, Sch Publ Hlth, BSL Lab Guangdong 3, Guangdong Prov Key Lab Trop Dis Res, 1023 South Shatai Rd, Guangzhou, Guangdong, Peoples R China
3.Southern Med Univ, Zhujiang Hosp, Dept Lab Med, 1023 South Shatai Rd, Guangzhou, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Shenzhen Key Lab Pathogen & Immun, State Key Discipline Infect Dis,Hosp 2, Shenzhen, Peoples R China
5.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin, Peoples R China
6.Beijing Inst Technol, Adv Res Inst Multidisciplinary Sci, Sch Life Sci, Key Lab Mol Med & Biotherapy, Beijing, Peoples R China
7.Univ Lahore, Inst Mol Biol & Biotechnol, Lahore, Pakistan
8.Southern Med Univ, Key Lab Infect Dis Res South China, Minist Educ, Guangzhou, Peoples R China

Ren, Zuning,Li, Mengjun,Chen, Jiayin,et al. Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus[J]. EMERGING MICROBES & INFECTIONS,2024,13(1).

Ren, Zuning.,Li, Mengjun.,Chen, Jiayin.,Gong, Xiaohua.,Song, Shuo.,...&Shen, Chenguang.(2024).Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus.EMERGING MICROBES & INFECTIONS,13(1).

Ren, Zuning,et al."Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus".EMERGING MICROBES & INFECTIONS 13.1(2024).