{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T01:11:02Z","timestamp":1779153062086,"version":"3.51.4"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":874,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["1\tZIA\tAI001009\t13"],"award-info":[{"award-number":["1\tZIA\tAI001009\t13"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,19]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    zygote antigen Pfs25. Using proteomic tools coupled with bulk immunosequencing data, we determined human antigen-binding fragment [F(ab\u2032)\n                    <jats:sub>2<\/jats:sub>\n                    ] peptide sequences from plasma IG of adults who received 4 doses of Pfs25-EPA\/Alhydrogel. Specifically, Pfs25 antigen-specific F(ab\u2032)\n                    <jats:sub>2<\/jats:sub>\n                    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\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    oocysts in infected mosquitoes by more than 80% at 100 \u03bcg\/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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.143471","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T12:28:59Z","timestamp":1602592139000},"source":"Crossref","is-referenced-by-count":16,"title":["Antimalarial antibody repertoire defined by plasma IG proteomics and single B cell IG sequencing"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-9996","authenticated-orcid":true,"given":"Camila H.","family":"Coelho","sequence":"first","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4584-4325","authenticated-orcid":true,"given":"Steven T.","family":"Nadakal","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Gonzales Hurtado","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Morrison","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4916-800X","authenticated-orcid":true,"given":"Jacob D.","family":"Galson","sequence":"additional","affiliation":[{"name":"University Children\u2019s Hospital Zurich, Zurich, Switzerland."},{"name":"Alchemab Therapeutics Ltd, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian","family":"Neal","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Wu","sequence":"additional","affiliation":[{"name":"PATH\u2019s Malaria Vaccine Initiative, Washington, DC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8860-0419","authenticated-orcid":true,"given":"C. Richter","family":"King","sequence":"additional","affiliation":[{"name":"PATH\u2019s Malaria Vaccine Initiative, Washington, DC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Price","sequence":"additional","affiliation":[{"name":"PATH\u2019s Malaria Vaccine Initiative, Washington, DC, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-2432","authenticated-orcid":true,"given":"Kazutoyo","family":"Miura","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector and Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Wong-Madden","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin Yai","family":"Alamou Doritchamou","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-5402","authenticated-orcid":true,"given":"David L.","family":"Narum","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryonne","family":"Snow-Smith","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7319-3371","authenticated-orcid":true,"given":"Marissa","family":"Vignali","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector and Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA."},{"name":"Adaptive Biotechnologies Corp, Seattle, Washington, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-2901","authenticated-orcid":true,"given":"Justin J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Seattle, Washington, 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R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. http:\/\/www.R-project.org\/ Accessed October 13, 2020"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/143471\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:51:27Z","timestamp":1779151887000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/143471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":48,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2020,11,19]]},"published-print":{"date-parts":[[2020,11,19]]}},"alternative-id":["10.1172\/jci.insight.143471"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.143471","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,19]]},"article-number":"e143471"}}