TY - JOUR
T1 - Three neutralizing mAbs induced by MPXV A29L protein recognizing different epitopes act synergistically against orthopoxvirus
AU - Li, Mengjun
AU - Ren, Zuning
AU - Wang, Yuelin
AU - Jiang, Yushan
AU - Yang, Minghui
AU - Li, Delin
AU - Chen, Jiayin
AU - Liang, Zuxin
AU - Lin, Yuhao
AU - Zeng, Zhujun
AU - Xu, Rui
AU - Wang, Yiting
AU - Zhu, Li
AU - Xiao, Weiwei
AU - Wu, Qinghua
AU - Zhang, Bao
AU - Wan, Chengsong
AU - Yang, Yang
AU - Wu, Bo
AU - Peng, Jie
AU - Zhao, Wei
AU - Shen, Chenguang
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - A29L protein
KW - MPXV
KW - Neutralizing mAbs
KW - orthopoxvirus
KW - synergistic effects
UR - http://www.scopus.com/inward/record.url?scp=85162902629&partnerID=8YFLogxK
U2 - 10.1080/22221751.2023.2223669
DO - 10.1080/22221751.2023.2223669
M3 - Article
C2 - 37288876
AN - SCOPUS:85162902629
SN - 2222-1751
VL - 12
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
IS - 2
M1 - 2223669
ER -