Chinese Scientists have made progress in monoclonal antibodies against mpox virus
Source：Zheng Zhang
2025-11-21
Professor Zheng Zhang leads a research team including Bin Ju from the Second Affiliated Hospital of Southern University of Science and Technology/Shenzhen Third People's Hospital, Professor Jing Xue from the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Professor Renhong Yan from the School of Medicine, Southern University of Science and Technology, and Professor Wenjie Tan from the Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention has collaborated to make progress in monoclonal antibodies against the mpox virus. The relevant research findings, titled "Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection", were published online in the journal Cell on August 26, 2025.
The global spread of the mpox outbreak has posed a severe threat to public health security, and the World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) twice. The A35 protein expressed on the enveloped virions (EVs) of the mpox virus is crucial for the intercellular transmission of the virus within the host, making it a potential effective target for antiviral drugs. Existing research progress has shown that antibodies targeting the A35 protein of the mpox virus or the homologous A33 protein of the vaccinia virus can protect mice against poxvirus infection to varying degrees. With the continuous advancement of research on anti-mpox virus monoclonal antibodies (mAbs), data on the protective efficacy of these antibodies in non-human primate (NHP) models is still lacking, and the molecular interaction mechanism by which antibodies recognize antigens also needs further clarification.
Two human monoclonal antibodies (mAbs), namely mAb 975 and mAb 981, identified in this study, can cross-recognize the A33 protein of vaccinia virus and the A35 protein of mpox virus. In the CAST/EiJ mouse infection model, the use of mAb 975 or mAb 981 alone exerted a significant protective effect against the mpox virus infection, including reducing the viral load in mouse plasma and various tissues, as well as alleviating pathological damage in the mouse spleen. In the rhesus macaque infection model, mAb 975 and mAb 981 also demonstrated protective effects, such as decreasing the viral load in rhesus macaque plasma, throat swabs, anal swabs, and various tissues. Notably, they could significantly inhibit the occurrence of skin lesions in rhesus macaques. In this study, high-resolution structures of the mAb 975-A35 complex and mAb 981-A35 complex were resolved using cryogenic electron microscopy (cryo-EM) technology, revealing the molecular mechanism by which the two antibodies recognize the mpox virus. This study further summarized the conserved characteristics of mAbs from different species binding to the similar antigen: Antibodies can form stable electrostatic interactions between the positively charged amino acids in the heavy-chain CDR3 region and the negatively charged amino acids in the middle part of the antigen dimer, inserting into the groove-like structure in the middle of the antigen dimer. Additionally, the hydrophobic amino acids in multiple CDR regions of the antibody can cooperate with the hydrophobic platform of the antigen dimer and the hydrophobic regions within the groove to stabilize the antibody-antigen complex.
This study confirmed that the two human anti-mpox virus mAbs can protect mice and rhesus macaques against mpox virus infection to a certain extent, providing candidates for the development of antibody drugs. The binding model between the antibodies and the mpox virus A35 dimer clarifies the molecular interaction mechanism and also offers important references for the design of next-generation vaccines.
This study was supported by the National Natural Science Foundation of China (Grant Nos.: 82025022, 82322040, 82222041, 82241068, 32422039) and other funding sources.
Article Link: https://www.cell.com/cell/abstract/S0092-8674(25)00919-5
The global spread of the mpox outbreak has posed a severe threat to public health security, and the World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) twice. The A35 protein expressed on the enveloped virions (EVs) of the mpox virus is crucial for the intercellular transmission of the virus within the host, making it a potential effective target for antiviral drugs. Existing research progress has shown that antibodies targeting the A35 protein of the mpox virus or the homologous A33 protein of the vaccinia virus can protect mice against poxvirus infection to varying degrees. With the continuous advancement of research on anti-mpox virus monoclonal antibodies (mAbs), data on the protective efficacy of these antibodies in non-human primate (NHP) models is still lacking, and the molecular interaction mechanism by which antibodies recognize antigens also needs further clarification.
Two human monoclonal antibodies (mAbs), namely mAb 975 and mAb 981, identified in this study, can cross-recognize the A33 protein of vaccinia virus and the A35 protein of mpox virus. In the CAST/EiJ mouse infection model, the use of mAb 975 or mAb 981 alone exerted a significant protective effect against the mpox virus infection, including reducing the viral load in mouse plasma and various tissues, as well as alleviating pathological damage in the mouse spleen. In the rhesus macaque infection model, mAb 975 and mAb 981 also demonstrated protective effects, such as decreasing the viral load in rhesus macaque plasma, throat swabs, anal swabs, and various tissues. Notably, they could significantly inhibit the occurrence of skin lesions in rhesus macaques. In this study, high-resolution structures of the mAb 975-A35 complex and mAb 981-A35 complex were resolved using cryogenic electron microscopy (cryo-EM) technology, revealing the molecular mechanism by which the two antibodies recognize the mpox virus. This study further summarized the conserved characteristics of mAbs from different species binding to the similar antigen: Antibodies can form stable electrostatic interactions between the positively charged amino acids in the heavy-chain CDR3 region and the negatively charged amino acids in the middle part of the antigen dimer, inserting into the groove-like structure in the middle of the antigen dimer. Additionally, the hydrophobic amino acids in multiple CDR regions of the antibody can cooperate with the hydrophobic platform of the antigen dimer and the hydrophobic regions within the groove to stabilize the antibody-antigen complex.
Figure: Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection
This study confirmed that the two human anti-mpox virus mAbs can protect mice and rhesus macaques against mpox virus infection to a certain extent, providing candidates for the development of antibody drugs. The binding model between the antibodies and the mpox virus A35 dimer clarifies the molecular interaction mechanism and also offers important references for the design of next-generation vaccines.
This study was supported by the National Natural Science Foundation of China (Grant Nos.: 82025022, 82322040, 82222041, 82241068, 32422039) and other funding sources.
Article Link: https://www.cell.com/cell/abstract/S0092-8674(25)00919-5
