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Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers

Smallpox, an epidemic disease caused by Orthopoxvirus variola, 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 engineere...

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Autores principales: Gu, Xiuling, Zhang, Yufan, Jiang, Wei, Wang, Dongfang, Lu, Jiao, Gu, Guanglei, Qin, Chengfeng, Fang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319751/
https://www.ncbi.nlm.nih.gov/pubmed/35891248
http://dx.doi.org/10.3390/vaccines10071084
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author Gu, Xiuling
Zhang, Yufan
Jiang, Wei
Wang, Dongfang
Lu, Jiao
Gu, Guanglei
Qin, Chengfeng
Fang, Min
author_facet Gu, Xiuling
Zhang, Yufan
Jiang, Wei
Wang, Dongfang
Lu, Jiao
Gu, Guanglei
Qin, Chengfeng
Fang, Min
author_sort Gu, Xiuling
collection PubMed
description Smallpox, an epidemic disease caused by Orthopoxvirus variola, 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.
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spelling pubmed-93197512022-07-27 Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers Gu, Xiuling Zhang, Yufan Jiang, Wei Wang, Dongfang Lu, Jiao Gu, Guanglei Qin, Chengfeng Fang, Min Vaccines (Basel) Article Smallpox, an epidemic disease caused by Orthopoxvirus variola, 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. MDPI 2022-07-06 /pmc/articles/PMC9319751/ /pubmed/35891248 http://dx.doi.org/10.3390/vaccines10071084 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gu, Xiuling
Zhang, Yufan
Jiang, Wei
Wang, Dongfang
Lu, Jiao
Gu, Guanglei
Qin, Chengfeng
Fang, Min
Protective Human Anti-Poxvirus Monoclonal Antibodies Are Generated from Rare Memory B Cells Isolated by Multicolor Antigen Tetramers
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319751/
https://www.ncbi.nlm.nih.gov/pubmed/35891248
http://dx.doi.org/10.3390/vaccines10071084
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