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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yevel Flores-Garcia, Lawrence T Wang, Minah Park, Beejan Asady, Azza H Idris, Neville K Kisalu, Christian Muñoz, Lais S Pereira, Joseph R Francica, Robert A Seder, Fidel Zavala
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4b2f0abc1d8945d0affa55beb09edf04
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4b2f0abc1d8945d0affa55beb09edf04
record_format	dspace
spelling	oai:doaj.org-article:4b2f0abc1d8945d0affa55beb09edf042021-12-02T19:59:53ZThe P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.1553-73661553-737410.1371/journal.ppat.1010042https://doaj.org/article/4b2f0abc1d8945d0affa55beb09edf042021-11-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1010042https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Rare 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.Yevel Flores-GarciaLawrence T WangMinah ParkBeejan AsadyAzza H IdrisNeville K KisaluChristian MuñozLais S PereiraJoseph R FrancicaRobert A SederFidel ZavalaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 11, p e1010042 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Yevel Flores-Garcia Lawrence T Wang Minah Park Beejan Asady Azza H Idris Neville K Kisalu Christian Muñoz Lais S Pereira Joseph R Francica Robert A Seder Fidel Zavala The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.
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	article
author	Yevel Flores-Garcia Lawrence T Wang Minah Park Beejan Asady Azza H Idris Neville K Kisalu Christian Muñoz Lais S Pereira Joseph R Francica Robert A Seder Fidel Zavala
author_facet	Yevel Flores-Garcia Lawrence T Wang Minah Park Beejan Asady Azza H Idris Neville K Kisalu Christian Muñoz Lais S Pereira Joseph R Francica Robert A Seder Fidel Zavala
author_sort	Yevel Flores-Garcia
title	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_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_sort	p. falciparum csp repeat region contains three distinct epitopes required for protection by antibodies in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4b2f0abc1d8945d0affa55beb09edf04
work_keys_str_mv	AT yevelfloresgarcia thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT lawrencetwang thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT minahpark thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT beejanasady thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT azzahidris thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT nevillekkisalu thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT christianmunoz thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT laisspereira thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT josephrfrancica thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT robertaseder thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT fidelzavala thepfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT yevelfloresgarcia pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT lawrencetwang pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT minahpark pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT beejanasady pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT azzahidris pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT nevillekkisalu pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT christianmunoz pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT laisspereira pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT josephrfrancica pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT robertaseder pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo AT fidelzavala pfalciparumcsprepeatregioncontainsthreedistinctepitopesrequiredforprotectionbyantibodiesinvivo
_version_	1718375719658061824

The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo.

Ejemplares similares