Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?
Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/4/473 |
| _version_ | 1827718141216555008 |
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| author | Matthew J. Burke Peter G. Stockley Joan Boyes |
| author_facet | Matthew J. Burke Peter G. Stockley Joan Boyes |
| author_sort | Matthew J. Burke |
| collection | DOAJ |
| description | Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses. |
| first_indexed | 2024-03-10T20:18:12Z |
| format | Article |
| id | doaj.art-47af81e58dd04b0c91598ba47842c26c |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T20:18:12Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-47af81e58dd04b0c91598ba47842c26c2023-11-19T22:21:55ZengMDPI AGViruses1999-49152020-04-0112447310.3390/v12040473Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?Matthew J. Burke0Peter G. Stockley1Joan Boyes2School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UKSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UKSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UKPotent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses.https://www.mdpi.com/1999-4915/12/4/473broadly neutralizing antibodiesultralong CDR H3bovine antibodiesantibody diversity |
| spellingShingle | Matthew J. Burke Peter G. Stockley Joan Boyes Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens? Viruses broadly neutralizing antibodies ultralong CDR H3 bovine antibodies antibody diversity |
| title | Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens? |
| title_full | Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens? |
| title_fullStr | Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens? |
| title_full_unstemmed | Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens? |
| title_short | Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens? |
| title_sort | broadly neutralizing bovine antibodies highly effective new tools against evasive pathogens |
| topic | broadly neutralizing antibodies ultralong CDR H3 bovine antibodies antibody diversity |
| url | https://www.mdpi.com/1999-4915/12/4/473 |
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