Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV – recently infec...
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| Formato: | Artigo |
| Idioma: | en_US |
| Publicado em: |
Royal Society of Chemistry
2016
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| Acesso em linha: | http://hdl.handle.net/1721.1/101221 https://orcid.org/0000-0003-1387-8472 https://orcid.org/0000-0003-0921-3144 |
| _version_ | 1826194730221830144 |
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| author | Tsioris, Konstantinos Gupta, Namita T. Ogunniyi, Adebola Oluwakayode Qian, Feng Yao, Yi Wang, Xiaomei Stern, Joel N. H. Chari, Raj Briggs, Adrian W. Clouser, Christopher R. Vigneault, Francois Church, George M. Garcia, Melissa N. Murray, Kristy O. Montgomery, Ruth R. Kleinstein, Steven H. Love, J. Christopher Zimnisky, Ross Martin Love, J. Christopher |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Tsioris, Konstantinos Gupta, Namita T. Ogunniyi, Adebola Oluwakayode Qian, Feng Yao, Yi Wang, Xiaomei Stern, Joel N. H. Chari, Raj Briggs, Adrian W. Clouser, Christopher R. Vigneault, Francois Church, George M. Garcia, Melissa N. Murray, Kristy O. Montgomery, Ruth R. Kleinstein, Steven H. Love, J. Christopher Zimnisky, Ross Martin Love, J. Christopher |
| author_sort | Tsioris, Konstantinos |
| collection | MIT |
| description | West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV – recently infected and post-convalescent subjects – and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases. |
| first_indexed | 2024-09-23T10:00:55Z |
| format | Article |
| id | mit-1721.1/101221 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:00:55Z |
| publishDate | 2016 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | mit-1721.1/1012212022-09-30T18:19:19Z Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing Tsioris, Konstantinos Gupta, Namita T. Ogunniyi, Adebola Oluwakayode Qian, Feng Yao, Yi Wang, Xiaomei Stern, Joel N. H. Chari, Raj Briggs, Adrian W. Clouser, Christopher R. Vigneault, Francois Church, George M. Garcia, Melissa N. Murray, Kristy O. Montgomery, Ruth R. Kleinstein, Steven H. Love, J. Christopher Zimnisky, Ross Martin Love, J. Christopher Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Tsioris, Konstantinos Ogunniyi, Adebola Oluwakayode Zimnisky, Ross Martin Love, J. Christopher West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV – recently infected and post-convalescent subjects – and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases. National Institutes of Health (U.S.) (U19AI089992) National Institutes of Health (U.S.) (AI091816) National Institutes of Health (U.S.) (R01AI104739) National Institutes of Health (U.S.) (1F32AI112359-01) National Institutes of Health (U.S.) (T15LM07056) Human Immunology Project Consortium Gillson Longenbaugh Foundation 2016-02-19T02:59:08Z 2016-02-19T02:59:08Z 2015-10 2015-06 Article http://purl.org/eprint/type/JournalArticle 1757-9694 1757-9708 http://hdl.handle.net/1721.1/101221 Tsioris, Konstantinos, Namita T. Gupta, Adebola O. Ogunniyi, Ross M. Zimnisky, Feng Qian, Yi Yao, Xiaomei Wang, et al. “Neutralizing Antibodies Against West Nile Virus Identified Directly from Human B Cells by Single-Cell Analysis and Next Generation Sequencing.” Integr. Biol. 7, no. 12 (2015): 1587–1597. © 2015 Royal Society of Chemistry https://orcid.org/0000-0003-1387-8472 https://orcid.org/0000-0003-0921-3144 en_US http://dx.doi.org/10.1039/c5ib00169b Integrative Biology Creative Commons Attribution 3.0 Unported licence http://creativecommons.org/licenses/by/3.0/ application/pdf Royal Society of Chemistry Royal Society of Chemistry |
| spellingShingle | Tsioris, Konstantinos Gupta, Namita T. Ogunniyi, Adebola Oluwakayode Qian, Feng Yao, Yi Wang, Xiaomei Stern, Joel N. H. Chari, Raj Briggs, Adrian W. Clouser, Christopher R. Vigneault, Francois Church, George M. Garcia, Melissa N. Murray, Kristy O. Montgomery, Ruth R. Kleinstein, Steven H. Love, J. Christopher Zimnisky, Ross Martin Love, J. Christopher Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing |
| title | Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing |
| title_full | Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing |
| title_fullStr | Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing |
| title_full_unstemmed | Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing |
| title_short | Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing |
| title_sort | neutralizing antibodies against west nile virus identified directly from human b cells by single cell analysis and next generation sequencing |
| url | http://hdl.handle.net/1721.1/101221 https://orcid.org/0000-0003-1387-8472 https://orcid.org/0000-0003-0921-3144 |
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