Cargando…

Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens

No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induc...

Descripción completa

Detalles Bibliográficos
Autores principales: Williams, Andrew R., Douglas, Alexander D., Miura, Kazutoyo, Illingworth, Joseph J., Choudhary, Prateek, Murungi, Linda M., Furze, Julie M., Diouf, Ababacar, Miotto, Olivo, Crosnier, Cécile, Wright, Gavin J., Kwiatkowski, Dominic P., Fairhurst, Rick M., Long, Carole A., Draper, Simon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493472/
https://www.ncbi.nlm.nih.gov/pubmed/23144611
http://dx.doi.org/10.1371/journal.ppat.1002991
_version_ 1782249267854835712
author Williams, Andrew R.
Douglas, Alexander D.
Miura, Kazutoyo
Illingworth, Joseph J.
Choudhary, Prateek
Murungi, Linda M.
Furze, Julie M.
Diouf, Ababacar
Miotto, Olivo
Crosnier, Cécile
Wright, Gavin J.
Kwiatkowski, Dominic P.
Fairhurst, Rick M.
Long, Carole A.
Draper, Simon J.
author_facet Williams, Andrew R.
Douglas, Alexander D.
Miura, Kazutoyo
Illingworth, Joseph J.
Choudhary, Prateek
Murungi, Linda M.
Furze, Julie M.
Diouf, Ababacar
Miotto, Olivo
Crosnier, Cécile
Wright, Gavin J.
Kwiatkowski, Dominic P.
Fairhurst, Rick M.
Long, Carole A.
Draper, Simon J.
author_sort Williams, Andrew R.
collection PubMed
description No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.
format Online
Article
Text
id pubmed-3493472
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-34934722012-11-09 Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens Williams, Andrew R. Douglas, Alexander D. Miura, Kazutoyo Illingworth, Joseph J. Choudhary, Prateek Murungi, Linda M. Furze, Julie M. Diouf, Ababacar Miotto, Olivo Crosnier, Cécile Wright, Gavin J. Kwiatkowski, Dominic P. Fairhurst, Rick M. Long, Carole A. Draper, Simon J. PLoS Pathog Research Article No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines. Public Library of Science 2012-11-08 /pmc/articles/PMC3493472/ /pubmed/23144611 http://dx.doi.org/10.1371/journal.ppat.1002991 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Williams, Andrew R.
Douglas, Alexander D.
Miura, Kazutoyo
Illingworth, Joseph J.
Choudhary, Prateek
Murungi, Linda M.
Furze, Julie M.
Diouf, Ababacar
Miotto, Olivo
Crosnier, Cécile
Wright, Gavin J.
Kwiatkowski, Dominic P.
Fairhurst, Rick M.
Long, Carole A.
Draper, Simon J.
Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens
title Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens
title_full Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens
title_fullStr Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens
title_full_unstemmed Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens
title_short Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens
title_sort enhancing blockade of plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against pfrh5 and other merozoite antigens
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493472/
https://www.ncbi.nlm.nih.gov/pubmed/23144611
http://dx.doi.org/10.1371/journal.ppat.1002991
work_keys_str_mv AT williamsandrewr enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT douglasalexanderd enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT miurakazutoyo enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT illingworthjosephj enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT choudharyprateek enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT murungilindam enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT furzejuliem enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT dioufababacar enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT miottoolivo enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT crosniercecile enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT wrightgavinj enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT kwiatkowskidominicp enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT fairhurstrickm enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT longcarolea enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens
AT drapersimonj enhancingblockadeofplasmodiumfalciparumerythrocyteinvasionassessingcombinationsofantibodiesagainstpfrh5andothermerozoiteantigens