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The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo
Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to wh...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601602/ https://www.ncbi.nlm.nih.gov/pubmed/34748617 http://dx.doi.org/10.1371/journal.ppat.1010042 |
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author | Flores-Garcia, Yevel Wang, Lawrence T. Park, Minah Asady, Beejan Idris, Azza H. Kisalu, Neville K. Muñoz, Christian Pereira, Lais S. Francica, Joseph R. Seder, Robert A. Zavala, Fidel |
author_facet | Flores-Garcia, Yevel Wang, Lawrence T. Park, Minah Asady, Beejan Idris, Azza H. Kisalu, Neville K. Muñoz, Christian Pereira, Lais S. Francica, Joseph R. Seder, Robert A. Zavala, Fidel |
author_sort | Flores-Garcia, Yevel |
collection | PubMed |
description | Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria. |
format | Online Article Text |
id | pubmed-8601602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86016022021-11-19 The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo Flores-Garcia, Yevel Wang, Lawrence T. Park, Minah Asady, Beejan Idris, Azza H. Kisalu, Neville K. Muñoz, Christian Pereira, Lais S. Francica, Joseph R. Seder, Robert A. Zavala, Fidel PLoS Pathog Research Article Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind the PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central repeats in vitro. The extent to which each of these epitopes is required for protection in vivo is unknown. Here, we assessed whether junction-, minor repeat- and central repeat-preferring human mAbs (CIS43, L9 and 317 respectively) bound and protected against in vivo challenge with transgenic P. berghei (Pb) SPZ expressing either PfCSP with the junction and minor repeats knocked out (KO), or PbCSP with the junction and minor repeats knocked in (KI). In vivo protection studies showed that the junction and minor repeats are necessary and sufficient for CIS43 and L9 to neutralize KO and KI SPZ, respectively. In contrast, 317 required major repeats for in vivo protection. These data establish that human mAbs can prevent malaria infection by targeting three different protective epitopes (NPDP, NVDP, NANP) in the PfCSP repeat region. This report will inform vaccine development and the use of mAbs to passively prevent malaria. Public Library of Science 2021-11-08 /pmc/articles/PMC8601602/ /pubmed/34748617 http://dx.doi.org/10.1371/journal.ppat.1010042 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Flores-Garcia, Yevel Wang, Lawrence T. Park, Minah Asady, Beejan Idris, Azza H. Kisalu, Neville K. Muñoz, Christian Pereira, Lais S. Francica, Joseph R. Seder, Robert A. Zavala, Fidel The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo |
title | The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo |
title_full | The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo |
title_fullStr | The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo |
title_full_unstemmed | The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo |
title_short | The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo |
title_sort | p. falciparum csp repeat region contains three distinct epitopes required for protection by antibodies in vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601602/ https://www.ncbi.nlm.nih.gov/pubmed/34748617 http://dx.doi.org/10.1371/journal.ppat.1010042 |
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