Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.

The clonally variant Plasmodium falciparum PfEMP1 adhesin is a virulence factor and a prime target of humoral immunity. It is encoded by a repertoire of functionally differentiated var genes, which display architectural diversity and allelic polymorphism. Their serological relationship is key to und...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Inès Vigan-Womas, Micheline Guillotte, Alexandre Juillerat, Cindy Vallieres, Anita Lewit-Bentley, Adama Tall, Laurence Baril, Graham A Bentley, Odile Mercereau-Puijalon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b66eaeb47b1f4584836b810bf1c4af48
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b66eaeb47b1f4584836b810bf1c4af48
record_format	dspace
spelling	oai:doaj.org-article:b66eaeb47b1f4584836b810bf1c4af482021-11-18T06:59:45ZAllelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.1932-620310.1371/journal.pone.0016544https://doaj.org/article/b66eaeb47b1f4584836b810bf1c4af482011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21298021/?tool=EBIhttps://doaj.org/toc/1932-6203The clonally variant Plasmodium falciparum PfEMP1 adhesin is a virulence factor and a prime target of humoral immunity. It is encoded by a repertoire of functionally differentiated var genes, which display architectural diversity and allelic polymorphism. Their serological relationship is key to understanding the evolutionary constraints on this gene family and rational vaccine design. Here, we investigated the Palo Alto/VarO and IT4/R29 and 3D7/PF13_003 parasites lines. VarO and R29 form rosettes with uninfected erythrocytes, a phenotype associated with severe malaria. They express an allelic Cys2/group A NTS-DBL1α(1) PfEMP1 domain implicated in rosetting, whose 3D7 ortholog is encoded by PF13_0003. Using these three recombinant NTS-DBL1α(1) domains, we elicited antibodies in mice that were used to develop monovariant cultures by panning selection. The 3D7/PF13_0003 parasites formed rosettes, revealing a correlation between sequence identity and virulence phenotype. The antibodies cross-reacted with the allelic domains in ELISA but only minimally with the Cys4/group B/C PFL1955w NTS-DBL1α. By contrast, they were variant-specific in surface seroreactivity of the monovariant-infected red cells by FACS analysis and in rosette-disruption assays. Thus, while ELISA can differentiate serogroups, surface reactivity assays define the more restrictive serotypes. Irrespective of cumulated exposure to infection, antibodies acquired by humans living in a malaria-endemic area also displayed a variant-specific surface reactivity. Although seroprevalence exceeded 90% for each rosetting line, the kinetics of acquisition of surface-reactive antibodies differed in the younger age groups. These data indicate that humans acquire an antibody repertoire to non-overlapping serotypes within a serogroup, consistent with an antibody-driven diversification pressure at the population level. In addition, the data provide important information for vaccine design, as production of a vaccine targeting rosetting PfEMP1 adhesins will require engineering to induce variant-transcending responses or combining multiple serotypes to elicit a broad spectrum of immunity.Inès Vigan-WomasMicheline GuillotteAlexandre JuilleratCindy VallieresAnita Lewit-BentleyAdama TallLaurence BarilGraham A BentleyOdile Mercereau-PuijalonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16544 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Inès Vigan-Womas Micheline Guillotte Alexandre Juillerat Cindy Vallieres Anita Lewit-Bentley Adama Tall Laurence Baril Graham A Bentley Odile Mercereau-Puijalon Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
description	The clonally variant Plasmodium falciparum PfEMP1 adhesin is a virulence factor and a prime target of humoral immunity. It is encoded by a repertoire of functionally differentiated var genes, which display architectural diversity and allelic polymorphism. Their serological relationship is key to understanding the evolutionary constraints on this gene family and rational vaccine design. Here, we investigated the Palo Alto/VarO and IT4/R29 and 3D7/PF13_003 parasites lines. VarO and R29 form rosettes with uninfected erythrocytes, a phenotype associated with severe malaria. They express an allelic Cys2/group A NTS-DBL1α(1) PfEMP1 domain implicated in rosetting, whose 3D7 ortholog is encoded by PF13_0003. Using these three recombinant NTS-DBL1α(1) domains, we elicited antibodies in mice that were used to develop monovariant cultures by panning selection. The 3D7/PF13_0003 parasites formed rosettes, revealing a correlation between sequence identity and virulence phenotype. The antibodies cross-reacted with the allelic domains in ELISA but only minimally with the Cys4/group B/C PFL1955w NTS-DBL1α. By contrast, they were variant-specific in surface seroreactivity of the monovariant-infected red cells by FACS analysis and in rosette-disruption assays. Thus, while ELISA can differentiate serogroups, surface reactivity assays define the more restrictive serotypes. Irrespective of cumulated exposure to infection, antibodies acquired by humans living in a malaria-endemic area also displayed a variant-specific surface reactivity. Although seroprevalence exceeded 90% for each rosetting line, the kinetics of acquisition of surface-reactive antibodies differed in the younger age groups. These data indicate that humans acquire an antibody repertoire to non-overlapping serotypes within a serogroup, consistent with an antibody-driven diversification pressure at the population level. In addition, the data provide important information for vaccine design, as production of a vaccine targeting rosetting PfEMP1 adhesins will require engineering to induce variant-transcending responses or combining multiple serotypes to elicit a broad spectrum of immunity.
format	article
author	Inès Vigan-Womas Micheline Guillotte Alexandre Juillerat Cindy Vallieres Anita Lewit-Bentley Adama Tall Laurence Baril Graham A Bentley Odile Mercereau-Puijalon
author_facet	Inès Vigan-Womas Micheline Guillotte Alexandre Juillerat Cindy Vallieres Anita Lewit-Bentley Adama Tall Laurence Baril Graham A Bentley Odile Mercereau-Puijalon
author_sort	Inès Vigan-Womas
title	Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
title_short	Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
title_full	Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
title_fullStr	Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
title_full_unstemmed	Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
title_sort	allelic diversity of the plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b66eaeb47b1f4584836b810bf1c4af48
work_keys_str_mv	AT inesviganwomas allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT michelineguillotte allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT alexandrejuillerat allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT cindyvallieres allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT anitalewitbentley allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT adamatall allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT laurencebaril allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT grahamabentley allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes AT odilemercereaupuijalon allelicdiversityoftheplasmodiumfalciparumerythrocytemembraneprotein1entailsvariantspecificredcellsurfaceepitopes
_version_	1718424127991185408

Allelic diversity of the Plasmodium falciparum erythrocyte membrane protein 1 entails variant-specific red cell surface epitopes.

Ejemplares similares