Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers
Smallpox, an epidemic disease caused by <i>Orthopoxvirus variola</i>, was eradicated worldwide through immunization. The immunization against smallpox was discontinued in 1980. However, incidences of monkeypox virus infection in humans have occurred sporadically, and there is also great...
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MDPI AG
2022-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/7/1084 |
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| author | Xiuling Gu Yufan Zhang Wei Jiang Dongfang Wang Jiao Lu Guanglei Gu Chengfeng Qin Min Fang |
| author_facet | Xiuling Gu Yufan Zhang Wei Jiang Dongfang Wang Jiao Lu Guanglei Gu Chengfeng Qin Min Fang |
| author_sort | Xiuling Gu |
| collection | DOAJ |
| description | Smallpox, an epidemic disease caused by <i>Orthopoxvirus variola</i>, was eradicated worldwide through immunization. The immunization against smallpox was discontinued in 1980. However, incidences of monkeypox virus infection in humans have occurred sporadically, and there is also great fear that engineered forms of poxvirus could be used as biological weapons. Therefore, monoclonal antibodies against poxvirus are urgently needed for the detection and treatment of poxvirus infection. The vaccinia virus’ extracellular envelope protein A33 is a potential candidate for a subunit vaccine. We used multi-fluorescence-labeled tetrameric A33 antigen to identify rare poxvirus-specific memory B cells from the PBMC of volunteers with vaccinia virus immunization more than 40 years ago. Despite extremely low frequencies of the poxvirus-specific memory B cells, we successfully sorted A33 tetramer-labeled single memory B cells and reconstructed the antibodies with the single-cell RT-PCR of the B-cell receptor. Among the monoclonal antibodies, one clone H2 exhibited high specificity and affinity with A33. H2 efficiently inhibited viral infection and spread in cells. Passive immunotherapy of H2 in mice protected mice from lethal infection when administered either prophylactically or therapeutically. These results suggest the potential of anti-A33 human-antibody-based detection and therapeutics for poxvirus infection. |
| first_indexed | 2024-03-09T10:10:50Z |
| format | Article |
| id | doaj.art-d874347fdd8645b19549f39e34e30ad2 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T10:10:50Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d874347fdd8645b19549f39e34e30ad22023-12-01T22:46:19ZengMDPI AGVaccines2076-393X2022-07-01107108410.3390/vaccines10071084Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen TetramersXiuling Gu0Yufan Zhang1Wei Jiang2Dongfang Wang3Jiao Lu4Guanglei Gu5Chengfeng Qin6Min Fang7CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaSmallpox, an epidemic disease caused by <i>Orthopoxvirus variola</i>, was eradicated worldwide through immunization. The immunization against smallpox was discontinued in 1980. However, incidences of monkeypox virus infection in humans have occurred sporadically, and there is also great fear that engineered forms of poxvirus could be used as biological weapons. Therefore, monoclonal antibodies against poxvirus are urgently needed for the detection and treatment of poxvirus infection. The vaccinia virus’ extracellular envelope protein A33 is a potential candidate for a subunit vaccine. We used multi-fluorescence-labeled tetrameric A33 antigen to identify rare poxvirus-specific memory B cells from the PBMC of volunteers with vaccinia virus immunization more than 40 years ago. Despite extremely low frequencies of the poxvirus-specific memory B cells, we successfully sorted A33 tetramer-labeled single memory B cells and reconstructed the antibodies with the single-cell RT-PCR of the B-cell receptor. Among the monoclonal antibodies, one clone H2 exhibited high specificity and affinity with A33. H2 efficiently inhibited viral infection and spread in cells. Passive immunotherapy of H2 in mice protected mice from lethal infection when administered either prophylactically or therapeutically. These results suggest the potential of anti-A33 human-antibody-based detection and therapeutics for poxvirus infection.https://www.mdpi.com/2076-393X/10/7/1084<i>Orthopoxvirus</i>subunit vaccineA33tetramerhuman antibody |
| spellingShingle | Xiuling Gu Yufan Zhang Wei Jiang Dongfang Wang Jiao Lu Guanglei Gu Chengfeng Qin Min Fang Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers Vaccines <i>Orthopoxvirus</i> subunit vaccine A33 tetramer human antibody |
| title | Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers |
| title_full | Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers |
| title_fullStr | Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers |
| title_full_unstemmed | Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers |
| title_short | Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers |
| title_sort | protective human anti poxvirus monoclonal antibodies are generated from rare memory b cells isolated by multicolor antigen tetramers |
| topic | <i>Orthopoxvirus</i> subunit vaccine A33 tetramer human antibody |
| url | https://www.mdpi.com/2076-393X/10/7/1084 |
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