Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus

Li, Mengjun1,2,3; Ren, Zuning1,2,3,4; Wang, Yuelin1,2,3; Jiang, Yushan1,2,3; Yang, Minghui5; Li, Delin6; Chen, Jiayin1,2,3; Liang, Zuxin1,2,3; Lin, Yuhao1,2,3; Zeng, Zhujun1,2,3,7; Xu, Rui7; Wang, Yiting8; Zhu, Li1,2,3; Xiao, Weiwei1,2,3; Wu, Qinghua1,2,3; Zhang, Bao1,2,3; Wan, Chengsong1,2,3; Yang, Yang9; Wu, Bo10; Peng, Jie4; Zhao, Wei1,2,3,11,12,13; Shen, Chenguang1,2,3,11,12,13

2023-12-08

10.1080/22221751.2023.2223669

EMERGING MICROBES & INFECTIONS   影响因子和分区

2222-1751

The worldwide outbreak of the monkeypox virus (MPXV) has become a "Public Health Emergency of International Concern" (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.

Neutralizing mAbs MPXV A29L protein synergistic effects orthopoxvirus

SCI

英语

其他

National Natural Science Foundation of China["32170939","82111530302"] ; Guangdong Basic and Applied Basic Research Foundation["2019A1515110675","2022B1515020075"] ; Shenzhen Science and Technology Innovation Commission for Research and Development Project[JCYJ20190809183205622] ; Guangdong Science and Technology Program key projects[2021B1212030014] ; Science and Technology Program of Guangzhou[202201011419]

Immunology ; Infectious Diseases ; Microbiology

Immunology ; Infectious Diseases ; Microbiology

WOS:001010203300001

TAYLOR & FRANCIS LTD

Web of Science

1.Sch Publ Hlth, Guangdong Prov Key Lab Trop Dis Res, BSL 3 Lab Guangdong, Guangzhou, Peoples R China
2.Zhujiang Hosp, Dept Lab Med, Guangzhou, Peoples R China
3.Southern Med Univ, Guangzhou, Peoples R China
4.Southern Med Univ, Nanfang Hosp, State Key Lab Organ Failure Res, Dept Infect Dis,Guangdong Prov Key Lab Viral Hepat, Guangzhou, Peoples R China
5.Beijing Inst Technol, Adv Res Inst Multidisciplinary Sci, Beijing, Peoples R China
6.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin, Peoples R China
7.Guangdong Prov Hosp Chinese Med, Med Lab Dept, Zhuhai, Peoples R China
8.Shenzhen Longhua Matern & Child Healthcare Hosp, Dept Lab, Shenzhen, Peoples R China
9.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Shenzhen Key Lab Pathogen & Immun, State Key Discipline Infect Dis,Hosp Affiliated 2, Shenzhen, Peoples R China
10.Hoyotek Biomed Co Ltd, Tianjin, Peoples R China
11.Sch Publ Hlth, BSL 3 Lab Guangdong, Guangdong Prov Key Lab Trop Dis Res, 1023 South Shatai Rd, Guangzhou, Guangdong, Peoples R China
12.Zhujiang Hosp, Dept Lab Med, 1023 South Shatai Rd, Guangzhou, Guangdong, Peoples R China
13.Southern Med Univ, 1023 South Shatai Rd, Guangzhou, Guangdong, Peoples R China

Li, Mengjun,Ren, Zuning,Wang, Yuelin,et al. Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus[J]. EMERGING MICROBES & INFECTIONS,2023,12(2).

Li, Mengjun.,Ren, Zuning.,Wang, Yuelin.,Jiang, Yushan.,Yang, Minghui.,...&Shen, Chenguang.(2023).Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus.EMERGING MICROBES & INFECTIONS,12(2).

Li, Mengjun,et al."Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus".EMERGING MICROBES & INFECTIONS 12.2(2023).