Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.

<h4>Background</h4>The objective was to evaluate the safety and immunogenicity of the AMA1-based malaria vaccine FMP2.1/AS02(A) in children exposed to seasonal falciparum malaria.<h4>Methodology/principal findings</h4>A Phase 1 double blind randomized controlled dose escalati...

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Main Authors: Mahamadou A Thera, Ogobara K Doumbo, Drissa Coulibaly, Matthew B Laurens, Abdoulaye K Kone, Ando B Guindo, Karim Traore, Mady Sissoko, Dapa A Diallo, Issa Diarra, Bourema Kouriba, Modibo Daou, Amagana Dolo, Mounirou Baby, Mahamadou S Sissoko, Issaka Sagara, Amadou Niangaly, Idrissa Traore, Ally Olotu, Olivier Godeaux, Amanda Leach, Marie-Claude Dubois, W Ripley Ballou, Joe Cohen, Darby Thompson, Tina Dube, Lorraine Soisson, Carter L Diggs, Shannon L Takala, Kirsten E Lyke, Brent House, David E Lanar, Sheetij Dutta, D Gray Heppner, Christopher V Plowe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-02-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009041&type=printable
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author Mahamadou A Thera
Ogobara K Doumbo
Drissa Coulibaly
Matthew B Laurens
Abdoulaye K Kone
Ando B Guindo
Karim Traore
Mady Sissoko
Dapa A Diallo
Issa Diarra
Bourema Kouriba
Modibo Daou
Amagana Dolo
Mounirou Baby
Mahamadou S Sissoko
Issaka Sagara
Amadou Niangaly
Idrissa Traore
Ally Olotu
Olivier Godeaux
Amanda Leach
Marie-Claude Dubois
W Ripley Ballou
Joe Cohen
Darby Thompson
Tina Dube
Lorraine Soisson
Carter L Diggs
Shannon L Takala
Kirsten E Lyke
Brent House
David E Lanar
Sheetij Dutta
D Gray Heppner
Christopher V Plowe
author_facet Mahamadou A Thera
Ogobara K Doumbo
Drissa Coulibaly
Matthew B Laurens
Abdoulaye K Kone
Ando B Guindo
Karim Traore
Mady Sissoko
Dapa A Diallo
Issa Diarra
Bourema Kouriba
Modibo Daou
Amagana Dolo
Mounirou Baby
Mahamadou S Sissoko
Issaka Sagara
Amadou Niangaly
Idrissa Traore
Ally Olotu
Olivier Godeaux
Amanda Leach
Marie-Claude Dubois
W Ripley Ballou
Joe Cohen
Darby Thompson
Tina Dube
Lorraine Soisson
Carter L Diggs
Shannon L Takala
Kirsten E Lyke
Brent House
David E Lanar
Sheetij Dutta
D Gray Heppner
Christopher V Plowe
author_sort Mahamadou A Thera
collection DOAJ
description <h4>Background</h4>The objective was to evaluate the safety and immunogenicity of the AMA1-based malaria vaccine FMP2.1/AS02(A) in children exposed to seasonal falciparum malaria.<h4>Methodology/principal findings</h4>A Phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02(A) is a recombinant protein (FMP2.1) based on apical membrane antigen 1 (AMA1) from the 3D7 clone of P. falciparum, formulated in the Adjuvant System AS02(A). The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). One hundred healthy Malian children aged 1-6 years were recruited into 3 cohorts and randomized to receive either 10 microg FMP2.1 in 0.1 mL AS02(A), or 25 microg FMP2.1 in 0.25 mL AS02(A), or 50 microg FMP2.1 50 microg in 0.5 mL AS02(A), or rabies vaccine. Three doses of vaccine were given at 0, 1 and 2 months, and children were followed for 1 year. Solicited symptoms were assessed for 7 days and unsolicited symptoms for 30 days after each vaccination. Serious adverse events were assessed throughout the study. Transient local pain and swelling were common and more frequent in all malaria vaccine dosage groups than in the comparator group, but were acceptable to parents of participants. Levels of anti-AMA1 antibodies measured by ELISA increased significantly (at least 100-fold compared to baseline) in all 3 malaria vaccine groups, and remained high during the year of follow up.<h4>Conclusion/significance</h4>The FMP2.1/AS02(A) vaccine had a good safety profile, was well-tolerated, and induced high and sustained antibody levels in malaria-exposed children. This malaria vaccine is being evaluated in a Phase 2 efficacy trial in children at this site.<h4>Trial registration</h4>ClinicalTrials.gov NCT00358332 [NCT00358332].
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spelling doaj-art-cc6d77a455c44be3828ff996e6e1400d2025-08-20T02:31:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-02-0152e904110.1371/journal.pone.0009041Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.Mahamadou A TheraOgobara K DoumboDrissa CoulibalyMatthew B LaurensAbdoulaye K KoneAndo B GuindoKarim TraoreMady SissokoDapa A DialloIssa DiarraBourema KouribaModibo DaouAmagana DoloMounirou BabyMahamadou S SissokoIssaka SagaraAmadou NiangalyIdrissa TraoreAlly OlotuOlivier GodeauxAmanda LeachMarie-Claude DuboisW Ripley BallouJoe CohenDarby ThompsonTina DubeLorraine SoissonCarter L DiggsShannon L TakalaKirsten E LykeBrent HouseDavid E LanarSheetij DuttaD Gray HeppnerChristopher V Plowe<h4>Background</h4>The objective was to evaluate the safety and immunogenicity of the AMA1-based malaria vaccine FMP2.1/AS02(A) in children exposed to seasonal falciparum malaria.<h4>Methodology/principal findings</h4>A Phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02(A) is a recombinant protein (FMP2.1) based on apical membrane antigen 1 (AMA1) from the 3D7 clone of P. falciparum, formulated in the Adjuvant System AS02(A). The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). One hundred healthy Malian children aged 1-6 years were recruited into 3 cohorts and randomized to receive either 10 microg FMP2.1 in 0.1 mL AS02(A), or 25 microg FMP2.1 in 0.25 mL AS02(A), or 50 microg FMP2.1 50 microg in 0.5 mL AS02(A), or rabies vaccine. Three doses of vaccine were given at 0, 1 and 2 months, and children were followed for 1 year. Solicited symptoms were assessed for 7 days and unsolicited symptoms for 30 days after each vaccination. Serious adverse events were assessed throughout the study. Transient local pain and swelling were common and more frequent in all malaria vaccine dosage groups than in the comparator group, but were acceptable to parents of participants. Levels of anti-AMA1 antibodies measured by ELISA increased significantly (at least 100-fold compared to baseline) in all 3 malaria vaccine groups, and remained high during the year of follow up.<h4>Conclusion/significance</h4>The FMP2.1/AS02(A) vaccine had a good safety profile, was well-tolerated, and induced high and sustained antibody levels in malaria-exposed children. This malaria vaccine is being evaluated in a Phase 2 efficacy trial in children at this site.<h4>Trial registration</h4>ClinicalTrials.gov NCT00358332 [NCT00358332].https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009041&type=printable
spellingShingle Mahamadou A Thera
Ogobara K Doumbo
Drissa Coulibaly
Matthew B Laurens
Abdoulaye K Kone
Ando B Guindo
Karim Traore
Mady Sissoko
Dapa A Diallo
Issa Diarra
Bourema Kouriba
Modibo Daou
Amagana Dolo
Mounirou Baby
Mahamadou S Sissoko
Issaka Sagara
Amadou Niangaly
Idrissa Traore
Ally Olotu
Olivier Godeaux
Amanda Leach
Marie-Claude Dubois
W Ripley Ballou
Joe Cohen
Darby Thompson
Tina Dube
Lorraine Soisson
Carter L Diggs
Shannon L Takala
Kirsten E Lyke
Brent House
David E Lanar
Sheetij Dutta
D Gray Heppner
Christopher V Plowe
Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.
PLoS ONE
title Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.
title_full Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.
title_fullStr Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.
title_full_unstemmed Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.
title_short Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.
title_sort safety and immunogenicity of an ama1 malaria vaccine in malian children results of a phase 1 randomized controlled trial
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009041&type=printable
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