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Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing
Plasma antimalarial Ab can mediate antiparasite immunity but has not previously been characterized at the molecular level. Here, we develop an innovative strategy to characterize humoral responses by integrating profiles of plasma immunoglobulins (IGs) or Abs with those expressed on B cells as part...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710313/ https://www.ncbi.nlm.nih.gov/pubmed/33048842 http://dx.doi.org/10.1172/jci.insight.143471 |
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author | Coelho, Camila H. Nadakal, Steven T. Gonzales Hurtado, Patricia Morrison, Robert Galson, Jacob D. Neal, Jillian Wu, Yimin King, C. Richter Price, Virginia Miura, Kazutoyo Wong-Madden, Sharon Alamou Doritchamou, Justin Yai Narum, David L. MacDonald, Nicholas J. Snow-Smith, Maryonne Vignali, Marissa Taylor, Justin J. Lefranc, Marie-Paule Trück, Johannes Long, Carole A. Sagara, Issaka Fried, Michal Duffy, Patrick E. |
author_facet | Coelho, Camila H. Nadakal, Steven T. Gonzales Hurtado, Patricia Morrison, Robert Galson, Jacob D. Neal, Jillian Wu, Yimin King, C. Richter Price, Virginia Miura, Kazutoyo Wong-Madden, Sharon Alamou Doritchamou, Justin Yai Narum, David L. MacDonald, Nicholas J. Snow-Smith, Maryonne Vignali, Marissa Taylor, Justin J. Lefranc, Marie-Paule Trück, Johannes Long, Carole A. Sagara, Issaka Fried, Michal Duffy, Patrick E. |
author_sort | Coelho, Camila H. |
collection | PubMed |
description | Plasma antimalarial Ab can mediate antiparasite immunity but has not previously been characterized at the molecular level. Here, we develop an innovative strategy to characterize humoral responses by integrating profiles of plasma immunoglobulins (IGs) or Abs with those expressed on B cells as part of the B cell receptor. We applied this strategy to define plasma IG and to determine variable (V) gene usage after vaccination with the Plasmodium falciparum zygote antigen Pfs25. Using proteomic tools coupled with bulk immunosequencing data, we determined human antigen-binding fragment [F(ab′)(2)] peptide sequences from plasma IG of adults who received 4 doses of Pfs25-EPA/Alhydrogel. Specifically, Pfs25 antigen-specific F(ab′)(2) peptides (Pfs25-IG) were aligned to cDNA sequences of IG heavy (IGH) chain complementarity determining region 3 from a data set generated by total peripheral B cell immunosequencing of the entire vaccinated population. IGHV4 was the most commonly identified IGHV subgroup of Pfs25-IG, a pattern that was corroborated by V heavy/V light chain sequencing of Pfs25-specific single B cells from 5 vaccinees and by matching plasma Pfs25-IG peptides and V-(D)-J sequences of Pfs25-specific single B cells from the same donor. Among 13 recombinant human mAbs generated from IG sequences of Pfs25-specific single B cells, a single IGHV4 mAb displayed strong neutralizing activity, reducing the number of P. falciparum oocysts in infected mosquitoes by more than 80% at 100 μg/mL. Our approach characterizes the human plasma Ab repertoire in response to the Pfs25-EPA/Alhydrogel vaccine and will be useful for studying circulating Abs in response to other vaccines as well as those induced during infections or autoimmune disorders. |
format | Online Article Text |
id | pubmed-7710313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-77103132020-12-04 Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing Coelho, Camila H. Nadakal, Steven T. Gonzales Hurtado, Patricia Morrison, Robert Galson, Jacob D. Neal, Jillian Wu, Yimin King, C. Richter Price, Virginia Miura, Kazutoyo Wong-Madden, Sharon Alamou Doritchamou, Justin Yai Narum, David L. MacDonald, Nicholas J. Snow-Smith, Maryonne Vignali, Marissa Taylor, Justin J. Lefranc, Marie-Paule Trück, Johannes Long, Carole A. Sagara, Issaka Fried, Michal Duffy, Patrick E. JCI Insight Technical Advance Plasma antimalarial Ab can mediate antiparasite immunity but has not previously been characterized at the molecular level. Here, we develop an innovative strategy to characterize humoral responses by integrating profiles of plasma immunoglobulins (IGs) or Abs with those expressed on B cells as part of the B cell receptor. We applied this strategy to define plasma IG and to determine variable (V) gene usage after vaccination with the Plasmodium falciparum zygote antigen Pfs25. Using proteomic tools coupled with bulk immunosequencing data, we determined human antigen-binding fragment [F(ab′)(2)] peptide sequences from plasma IG of adults who received 4 doses of Pfs25-EPA/Alhydrogel. Specifically, Pfs25 antigen-specific F(ab′)(2) peptides (Pfs25-IG) were aligned to cDNA sequences of IG heavy (IGH) chain complementarity determining region 3 from a data set generated by total peripheral B cell immunosequencing of the entire vaccinated population. IGHV4 was the most commonly identified IGHV subgroup of Pfs25-IG, a pattern that was corroborated by V heavy/V light chain sequencing of Pfs25-specific single B cells from 5 vaccinees and by matching plasma Pfs25-IG peptides and V-(D)-J sequences of Pfs25-specific single B cells from the same donor. Among 13 recombinant human mAbs generated from IG sequences of Pfs25-specific single B cells, a single IGHV4 mAb displayed strong neutralizing activity, reducing the number of P. falciparum oocysts in infected mosquitoes by more than 80% at 100 μg/mL. Our approach characterizes the human plasma Ab repertoire in response to the Pfs25-EPA/Alhydrogel vaccine and will be useful for studying circulating Abs in response to other vaccines as well as those induced during infections or autoimmune disorders. American Society for Clinical Investigation 2020-11-19 /pmc/articles/PMC7710313/ /pubmed/33048842 http://dx.doi.org/10.1172/jci.insight.143471 Text en © 2020 Coelho et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Technical Advance Coelho, Camila H. Nadakal, Steven T. Gonzales Hurtado, Patricia Morrison, Robert Galson, Jacob D. Neal, Jillian Wu, Yimin King, C. Richter Price, Virginia Miura, Kazutoyo Wong-Madden, Sharon Alamou Doritchamou, Justin Yai Narum, David L. MacDonald, Nicholas J. Snow-Smith, Maryonne Vignali, Marissa Taylor, Justin J. Lefranc, Marie-Paule Trück, Johannes Long, Carole A. Sagara, Issaka Fried, Michal Duffy, Patrick E. Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing |
title | Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing |
title_full | Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing |
title_fullStr | Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing |
title_full_unstemmed | Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing |
title_short | Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing |
title_sort | antimalarial antibody repertoire defined by plasma ig proteomics and single b cell ig sequencing |
topic | Technical Advance |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710313/ https://www.ncbi.nlm.nih.gov/pubmed/33048842 http://dx.doi.org/10.1172/jci.insight.143471 |
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