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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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