A tool for evaluating heterogeneity in avidity of polyclonal antibodies
Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution...
| 出版年: | Frontiers in Immunology |
|---|---|
| 主要な著者: | , , , , , , , , , , , , , , , , , |
| フォーマット: | 論文 |
| 言語: | 英語 |
| 出版事項: |
Frontiers Media S.A.
2023-02-01
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| 主題: | |
| オンライン･アクセス: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049673/full |
| _version_ | 1857051707639332864 |
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| author | Kan Li Kan Li Michael Dodds Rachel L. Spreng Milite Abraha Milite Abraha Richard H. C. Huntwork Richard H. C. Huntwork Lindsay C. Dahora Lindsay C. Dahora Tinashe Nyanhete Tinashe Nyanhete Sheetij Dutta Ulrike Wille-Reece Erik Jongert Katie J. Ewer Adrian V. S. Hill Adrian V. S. Hill Celina Jin Jennifer Hill Andrew J. Pollard Andrew J. Pollard S. Munir Alam S. Munir Alam Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras S. Moses Dennison S. Moses Dennison |
| author_facet | Kan Li Kan Li Michael Dodds Rachel L. Spreng Milite Abraha Milite Abraha Richard H. C. Huntwork Richard H. C. Huntwork Lindsay C. Dahora Lindsay C. Dahora Tinashe Nyanhete Tinashe Nyanhete Sheetij Dutta Ulrike Wille-Reece Erik Jongert Katie J. Ewer Adrian V. S. Hill Adrian V. S. Hill Celina Jin Jennifer Hill Andrew J. Pollard Andrew J. Pollard S. Munir Alam S. Munir Alam Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras S. Moses Dennison S. Moses Dennison |
| author_sort | Kan Li |
| collection | DOAJ |
| container_title | Frontiers in Immunology |
| description | Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution tool (PAART) for use with label-free techniques, such as surface plasmon resonance and biolayer interferometry, that can monitor pAb-antigen interactions in real time to measure dissociation rate constant (kd) for defining avidity. PAART utilizes a sum of exponentials model to fit the dissociation time-courses of pAb-antigens interactions and resolve multiple kd contributing to the overall dissociation. Each kd value of pAb dissociation resolved by PAART corresponds to a group of antibodies with similar avidity. PAART is designed to identify the minimum number of exponentials required to explain the dissociation course and guards against overfitting of data by parsimony selection of best model using Akaike information criterion. Validation of PAART was performed using binary mixtures of monoclonal antibodies of same specificity but differing in kd of the interaction with their epitope. We applied PAART to examine the heterogeneity in avidities of pAb from malaria and typhoid vaccinees, and individuals living with HIV-1 that naturally control the viral load. In many cases, two to three kd were dissected indicating the heterogeneity of pAb avidities. We showcase examples of affinity maturation of vaccine induced pAb responses at component level and enhanced resolution of heterogeneity in avidity when antigen-binding fragments (Fab) are used instead of polyclonal IgG antibodies. The utility of PAART can be manifold in examining circulating pAb characteristics and could inform vaccine strategies aimed to guide the host humoral immune response. |
| format | Article |
| id | doaj-art-daa2eeeb0ae945ebaa3a3cfd1fe010ec |
| institution | Directory of Open Access Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| spelling | doaj-art-daa2eeeb0ae945ebaa3a3cfd1fe010ec2025-08-19T19:32:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.10496731049673A tool for evaluating heterogeneity in avidity of polyclonal antibodiesKan Li0Kan Li1Michael Dodds2Rachel L. Spreng3Milite Abraha4Milite Abraha5Richard H. C. Huntwork6Richard H. C. Huntwork7Lindsay C. Dahora8Lindsay C. Dahora9Tinashe Nyanhete10Tinashe Nyanhete11Sheetij Dutta12Ulrike Wille-Reece13Erik Jongert14Katie J. Ewer15Adrian V. S. Hill16Adrian V. S. Hill17Celina Jin18Jennifer Hill19Andrew J. Pollard20Andrew J. Pollard21S. Munir Alam22S. Munir Alam23Georgia D. Tomaras24Georgia D. Tomaras25Georgia D. Tomaras26Georgia D. Tomaras27Georgia D. Tomaras28S. Moses Dennison29S. Moses Dennison30Center for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Surgery, Duke University, Durham, NC, United StatesIntegrated Drug Development, Certara, Seattle, WA, United StatesDuke Human Vaccine Institute, Duke University, Durham, NC, United StatesCenter for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Surgery, Duke University, Durham, NC, United StatesCenter for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Surgery, Duke University, Durham, NC, United StatesCenter for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Immunology, Duke University, Durham, NC, United StatesCenter for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Immunology, Duke University, Durham, NC, United StatesStructural Vaccinology Lab, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United StatesPATH's Center for Vaccine Innovation and Access, Washington, DC, United StatesGSK Vaccines, Rixensart, BelgiumThe Jenner Institute, University of Oxford, Oxford, United KingdomThe Jenner Institute, University of Oxford, Oxford, United Kingdom0National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Center, Oxford, United Kingdom1Oxford Vaccine Group and Department of Pediatrics, University of Oxford, Oxford, United Kingdom1Oxford Vaccine Group and Department of Pediatrics, University of Oxford, Oxford, United Kingdom0National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Center, Oxford, United Kingdom1Oxford Vaccine Group and Department of Pediatrics, University of Oxford, Oxford, United KingdomDuke Human Vaccine Institute, Duke University, Durham, NC, United States2Department of Pathology, Duke University, Durham, NC, United StatesCenter for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Surgery, Duke University, Durham, NC, United StatesDuke Human Vaccine Institute, Duke University, Durham, NC, United StatesDepartment of Immunology, Duke University, Durham, NC, United States3Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, United StatesCenter for Human Systems Immunology, Duke University, Durham, NC, United StatesDepartment of Surgery, Duke University, Durham, NC, United StatesDiversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution tool (PAART) for use with label-free techniques, such as surface plasmon resonance and biolayer interferometry, that can monitor pAb-antigen interactions in real time to measure dissociation rate constant (kd) for defining avidity. PAART utilizes a sum of exponentials model to fit the dissociation time-courses of pAb-antigens interactions and resolve multiple kd contributing to the overall dissociation. Each kd value of pAb dissociation resolved by PAART corresponds to a group of antibodies with similar avidity. PAART is designed to identify the minimum number of exponentials required to explain the dissociation course and guards against overfitting of data by parsimony selection of best model using Akaike information criterion. Validation of PAART was performed using binary mixtures of monoclonal antibodies of same specificity but differing in kd of the interaction with their epitope. We applied PAART to examine the heterogeneity in avidities of pAb from malaria and typhoid vaccinees, and individuals living with HIV-1 that naturally control the viral load. In many cases, two to three kd were dissected indicating the heterogeneity of pAb avidities. We showcase examples of affinity maturation of vaccine induced pAb responses at component level and enhanced resolution of heterogeneity in avidity when antigen-binding fragments (Fab) are used instead of polyclonal IgG antibodies. The utility of PAART can be manifold in examining circulating pAb characteristics and could inform vaccine strategies aimed to guide the host humoral immune response.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049673/fulldissociation rateaviditybinningpolyclonal antibodiesTyphimRTS,S/AS01 |
| spellingShingle | Kan Li Kan Li Michael Dodds Rachel L. Spreng Milite Abraha Milite Abraha Richard H. C. Huntwork Richard H. C. Huntwork Lindsay C. Dahora Lindsay C. Dahora Tinashe Nyanhete Tinashe Nyanhete Sheetij Dutta Ulrike Wille-Reece Erik Jongert Katie J. Ewer Adrian V. S. Hill Adrian V. S. Hill Celina Jin Jennifer Hill Andrew J. Pollard Andrew J. Pollard S. Munir Alam S. Munir Alam Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras Georgia D. Tomaras S. Moses Dennison S. Moses Dennison A tool for evaluating heterogeneity in avidity of polyclonal antibodies dissociation rate avidity binning polyclonal antibodies Typhim RTS,S/AS01 |
| title | A tool for evaluating heterogeneity in avidity of polyclonal antibodies |
| title_full | A tool for evaluating heterogeneity in avidity of polyclonal antibodies |
| title_fullStr | A tool for evaluating heterogeneity in avidity of polyclonal antibodies |
| title_full_unstemmed | A tool for evaluating heterogeneity in avidity of polyclonal antibodies |
| title_short | A tool for evaluating heterogeneity in avidity of polyclonal antibodies |
| title_sort | tool for evaluating heterogeneity in avidity of polyclonal antibodies |
| topic | dissociation rate avidity binning polyclonal antibodies Typhim RTS,S/AS01 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049673/full |
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