Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.

<h4>Background</h4>Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we invest...

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Autores principales:	Christian Roussilhon, Claude Oeuvray, Christine Müller-Graf, Adama Tall, Christophe Rogier, Jean-François Trape, Michael Theisen, Aissatou Balde, Jean-Louis Pérignon, Pierre Druilhe
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2007
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/ae1745a14b3e4860b819082f466237b5
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spelling	oai:doaj.org-article:ae1745a14b3e4860b819082f466237b52021-11-25T05:36:43ZLong-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.1549-12771549-167610.1371/journal.pmed.0040320https://doaj.org/article/ae1745a14b3e4860b819082f466237b52007-11-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.0040320https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates.<h4>Methods and findings</h4>We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved.<h4>Conclusions</h4>Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.Christian RoussilhonClaude OeuvrayChristine Müller-GrafAdama TallChristophe RogierJean-François TrapeMichael TheisenAissatou BaldeJean-Louis PérignonPierre DruilhePublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 4, Iss 11, p e320 (2007)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Christian Roussilhon Claude Oeuvray Christine Müller-Graf Adama Tall Christophe Rogier Jean-François Trape Michael Theisen Aissatou Balde Jean-Louis Pérignon Pierre Druilhe Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.
description	<h4>Background</h4>Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates.<h4>Methods and findings</h4>We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved.<h4>Conclusions</h4>Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.
format	article
author	Christian Roussilhon Claude Oeuvray Christine Müller-Graf Adama Tall Christophe Rogier Jean-François Trape Michael Theisen Aissatou Balde Jean-Louis Pérignon Pierre Druilhe
author_facet	Christian Roussilhon Claude Oeuvray Christine Müller-Graf Adama Tall Christophe Rogier Jean-François Trape Michael Theisen Aissatou Balde Jean-Louis Pérignon Pierre Druilhe
author_sort	Christian Roussilhon
title	Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.
title_short	Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.
title_full	Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.
title_fullStr	Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.
title_full_unstemmed	Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.
title_sort	long-term clinical protection from falciparum malaria is strongly associated with igg3 antibodies to merozoite surface protein 3.
publisher	Public Library of Science (PLoS)
publishDate	2007
url	https://doaj.org/article/ae1745a14b3e4860b819082f466237b5
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Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3.

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