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Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein

BACKGROUND: Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a dis...

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Autores principales: Grüner, Anne Charlotte, Mauduit, Marjorie, Tewari, Rita, Romero, Jackeline F., Depinay, Nadya, Kayibanda, Michèle, Lallemand, Eliette, Chavatte, Jean-Marc, Crisanti, Andrea, Sinnis, Photini, Mazier, Dominique, Corradin, Giampietro, Snounou, Georges, Rénia, Laurent
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147056/
https://www.ncbi.nlm.nih.gov/pubmed/18159254
http://dx.doi.org/10.1371/journal.pone.0001371
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author Grüner, Anne Charlotte
Mauduit, Marjorie
Tewari, Rita
Romero, Jackeline F.
Depinay, Nadya
Kayibanda, Michèle
Lallemand, Eliette
Chavatte, Jean-Marc
Crisanti, Andrea
Sinnis, Photini
Mazier, Dominique
Corradin, Giampietro
Snounou, Georges
Rénia, Laurent
author_facet Grüner, Anne Charlotte
Mauduit, Marjorie
Tewari, Rita
Romero, Jackeline F.
Depinay, Nadya
Kayibanda, Michèle
Lallemand, Eliette
Chavatte, Jean-Marc
Crisanti, Andrea
Sinnis, Photini
Mazier, Dominique
Corradin, Giampietro
Snounou, Georges
Rénia, Laurent
author_sort Grüner, Anne Charlotte
collection PubMed
description BACKGROUND: Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection. The circumsporozoite protein (CSP), an important component of the sporozoite's surface, remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic stages. Difficulties in developing CSP-based vaccines that reproduce the levels of protection afforded by radiation-attenuated sporozoites have led us to question the role of CSP in the acquisition of sterile immunity. We have used a parasite transgenic for the CSP because it allowed us to test whether a major immunodominant Plasmodium antigen is indeed needed for the induction of sterile protective immunity against infection. METHODOLOGY/MAIN FINDINGS: We employed a P. berghei parasite line that expresses a heterologous CSP from P. falciparum in order to assess the role of the CSP in the protection conferred by vaccination with radiation-attenuated P. berghei parasites. Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge. CONCLUSIONS: We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria. From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.
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spelling pubmed-21470562007-12-26 Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein Grüner, Anne Charlotte Mauduit, Marjorie Tewari, Rita Romero, Jackeline F. Depinay, Nadya Kayibanda, Michèle Lallemand, Eliette Chavatte, Jean-Marc Crisanti, Andrea Sinnis, Photini Mazier, Dominique Corradin, Giampietro Snounou, Georges Rénia, Laurent PLoS One Research Article BACKGROUND: Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection. The circumsporozoite protein (CSP), an important component of the sporozoite's surface, remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic stages. Difficulties in developing CSP-based vaccines that reproduce the levels of protection afforded by radiation-attenuated sporozoites have led us to question the role of CSP in the acquisition of sterile immunity. We have used a parasite transgenic for the CSP because it allowed us to test whether a major immunodominant Plasmodium antigen is indeed needed for the induction of sterile protective immunity against infection. METHODOLOGY/MAIN FINDINGS: We employed a P. berghei parasite line that expresses a heterologous CSP from P. falciparum in order to assess the role of the CSP in the protection conferred by vaccination with radiation-attenuated P. berghei parasites. Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge. CONCLUSIONS: We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria. From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development. Public Library of Science 2007-12-26 /pmc/articles/PMC2147056/ /pubmed/18159254 http://dx.doi.org/10.1371/journal.pone.0001371 Text en Grüner et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grüner, Anne Charlotte
Mauduit, Marjorie
Tewari, Rita
Romero, Jackeline F.
Depinay, Nadya
Kayibanda, Michèle
Lallemand, Eliette
Chavatte, Jean-Marc
Crisanti, Andrea
Sinnis, Photini
Mazier, Dominique
Corradin, Giampietro
Snounou, Georges
Rénia, Laurent
Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein
title Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein
title_full Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein
title_fullStr Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein
title_full_unstemmed Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein
title_short Sterile Protection against Malaria Is Independent of Immune Responses to the Circumsporozoite Protein
title_sort sterile protection against malaria is independent of immune responses to the circumsporozoite protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147056/
https://www.ncbi.nlm.nih.gov/pubmed/18159254
http://dx.doi.org/10.1371/journal.pone.0001371
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