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Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites

Adjuvants have been essential to malaria vaccine development, but their impact on the vaccine-induced antibody repertoire is poorly understood. Here, we used cDNA sequences from antigen-specific single memory B cells to express 132 recombinant human anti-Pfs230 monoclonal antibodies (mAbs). Alhydrog...

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Autores principales: Coelho, Camila H., Marquez, Susanna, Tentokam, Bergeline C. Nguemwo, Berhe, Anne D., Miura, Kazutoyo, Long, Carole A., Sagara, Issaka, Healy, Sara, Kleinstein, Steven H., Duffy, Patrick E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541113/
https://www.ncbi.nlm.nih.gov/pubmed/37781572
http://dx.doi.org/10.1101/2023.08.01.551554
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author Coelho, Camila H.
Marquez, Susanna
Tentokam, Bergeline C. Nguemwo
Berhe, Anne D.
Miura, Kazutoyo
Long, Carole A.
Sagara, Issaka
Healy, Sara
Kleinstein, Steven H.
Duffy, Patrick E.
author_facet Coelho, Camila H.
Marquez, Susanna
Tentokam, Bergeline C. Nguemwo
Berhe, Anne D.
Miura, Kazutoyo
Long, Carole A.
Sagara, Issaka
Healy, Sara
Kleinstein, Steven H.
Duffy, Patrick E.
author_sort Coelho, Camila H.
collection PubMed
description Adjuvants have been essential to malaria vaccine development, but their impact on the vaccine-induced antibody repertoire is poorly understood. Here, we used cDNA sequences from antigen-specific single memory B cells to express 132 recombinant human anti-Pfs230 monoclonal antibodies (mAbs). Alhydrogel(®)-induced mAbs demonstrated higher binding to Pfs230D1, although functional activity was similar between adjuvants. All Alhydrogel(®) mAbs using IGHV1–69 gene bound to recombinant Pfs230D1, but none blocked parasite transmission to mosquitoes; similarly, no AS01 mAb using IGHV1–69 blocked transmission. Functional mAbs from both Alhydrogel(®) and AS01 vaccines used IGHV3–21 and IGHV3–30 genes. Antibodies with the longest CDR3 sequences were associated with binding but not functional activity. This study assesses adjuvant effects on antibody clonotype diversity during malaria vaccination.
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spelling pubmed-105411132023-10-01 Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites Coelho, Camila H. Marquez, Susanna Tentokam, Bergeline C. Nguemwo Berhe, Anne D. Miura, Kazutoyo Long, Carole A. Sagara, Issaka Healy, Sara Kleinstein, Steven H. Duffy, Patrick E. bioRxiv Article Adjuvants have been essential to malaria vaccine development, but their impact on the vaccine-induced antibody repertoire is poorly understood. Here, we used cDNA sequences from antigen-specific single memory B cells to express 132 recombinant human anti-Pfs230 monoclonal antibodies (mAbs). Alhydrogel(®)-induced mAbs demonstrated higher binding to Pfs230D1, although functional activity was similar between adjuvants. All Alhydrogel(®) mAbs using IGHV1–69 gene bound to recombinant Pfs230D1, but none blocked parasite transmission to mosquitoes; similarly, no AS01 mAb using IGHV1–69 blocked transmission. Functional mAbs from both Alhydrogel(®) and AS01 vaccines used IGHV3–21 and IGHV3–30 genes. Antibodies with the longest CDR3 sequences were associated with binding but not functional activity. This study assesses adjuvant effects on antibody clonotype diversity during malaria vaccination. Cold Spring Harbor Laboratory 2023-08-03 /pmc/articles/PMC10541113/ /pubmed/37781572 http://dx.doi.org/10.1101/2023.08.01.551554 Text en https://creativecommons.org/publicdomain/zero/1.0/This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Article
Coelho, Camila H.
Marquez, Susanna
Tentokam, Bergeline C. Nguemwo
Berhe, Anne D.
Miura, Kazutoyo
Long, Carole A.
Sagara, Issaka
Healy, Sara
Kleinstein, Steven H.
Duffy, Patrick E.
Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites
title Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites
title_full Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites
title_fullStr Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites
title_full_unstemmed Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites
title_short Antibody gene features associated with binding and functional activity in vaccine-derived human mAbs targeting malaria parasites
title_sort antibody gene features associated with binding and functional activity in vaccine-derived human mabs targeting malaria parasites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541113/
https://www.ncbi.nlm.nih.gov/pubmed/37781572
http://dx.doi.org/10.1101/2023.08.01.551554
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