Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

<h4>Background</h4>The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.<h4>Methodology/principal findings</h4>A phase 1 double blind randomized controlled...

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Main Authors: Mahamadou A Thera, Ogobara K Doumbo, Drissa Coulibaly, Dapa A Diallo, Abdoulaye K Kone, Ando B Guindo, Karim Traore, Alassane Dicko, Issaka Sagara, Mahamadou S Sissoko, Mounirou Baby, Mady Sissoko, Issa Diarra, Amadou Niangaly, Amagana Dolo, Modibo Daou, Sory I Diawara, D Gray Heppner, V Ann Stewart, Evelina Angov, Elke S Bergmann-Leitner, David E Lanar, Sheetij Dutta, Lorraine Soisson, Carter L Diggs, Amanda Leach, Alex Owusu, Marie-Claude Dubois, Joe Cohen, Jason N Nixon, Aric Gregson, Shannon L Takala, Kirsten E Lyke, Christopher V Plowe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001465&type=printable
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author Mahamadou A Thera
Ogobara K Doumbo
Drissa Coulibaly
Dapa A Diallo
Abdoulaye K Kone
Ando B Guindo
Karim Traore
Alassane Dicko
Issaka Sagara
Mahamadou S Sissoko
Mounirou Baby
Mady Sissoko
Issa Diarra
Amadou Niangaly
Amagana Dolo
Modibo Daou
Sory I Diawara
D Gray Heppner
V Ann Stewart
Evelina Angov
Elke S Bergmann-Leitner
David E Lanar
Sheetij Dutta
Lorraine Soisson
Carter L Diggs
Amanda Leach
Alex Owusu
Marie-Claude Dubois
Joe Cohen
Jason N Nixon
Aric Gregson
Shannon L Takala
Kirsten E Lyke
Christopher V Plowe
author_facet Mahamadou A Thera
Ogobara K Doumbo
Drissa Coulibaly
Dapa A Diallo
Abdoulaye K Kone
Ando B Guindo
Karim Traore
Alassane Dicko
Issaka Sagara
Mahamadou S Sissoko
Mounirou Baby
Mady Sissoko
Issa Diarra
Amadou Niangaly
Amagana Dolo
Modibo Daou
Sory I Diawara
D Gray Heppner
V Ann Stewart
Evelina Angov
Elke S Bergmann-Leitner
David E Lanar
Sheetij Dutta
Lorraine Soisson
Carter L Diggs
Amanda Leach
Alex Owusu
Marie-Claude Dubois
Joe Cohen
Jason N Nixon
Aric Gregson
Shannon L Takala
Kirsten E Lyke
Christopher V Plowe
author_sort Mahamadou A Thera
collection DOAJ
description <h4>Background</h4>The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal 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/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.<h4>Conclusion/significance</h4>The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.
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spelling doaj-art-15ab68b51b8a4e868fb076837e1ef8a92025-08-20T02:00:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0131e146510.1371/journal.pone.0001465Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.Mahamadou A TheraOgobara K DoumboDrissa CoulibalyDapa A DialloAbdoulaye K KoneAndo B GuindoKarim TraoreAlassane DickoIssaka SagaraMahamadou S SissokoMounirou BabyMady SissokoIssa DiarraAmadou NiangalyAmagana DoloModibo DaouSory I DiawaraD Gray HeppnerV Ann StewartEvelina AngovElke S Bergmann-LeitnerDavid E LanarSheetij DuttaLorraine SoissonCarter L DiggsAmanda LeachAlex OwusuMarie-Claude DuboisJoe CohenJason N NixonAric GregsonShannon L TakalaKirsten E LykeChristopher V Plowe<h4>Background</h4>The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal 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/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.<h4>Conclusion/significance</h4>The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001465&type=printable
spellingShingle Mahamadou A Thera
Ogobara K Doumbo
Drissa Coulibaly
Dapa A Diallo
Abdoulaye K Kone
Ando B Guindo
Karim Traore
Alassane Dicko
Issaka Sagara
Mahamadou S Sissoko
Mounirou Baby
Mady Sissoko
Issa Diarra
Amadou Niangaly
Amagana Dolo
Modibo Daou
Sory I Diawara
D Gray Heppner
V Ann Stewart
Evelina Angov
Elke S Bergmann-Leitner
David E Lanar
Sheetij Dutta
Lorraine Soisson
Carter L Diggs
Amanda Leach
Alex Owusu
Marie-Claude Dubois
Joe Cohen
Jason N Nixon
Aric Gregson
Shannon L Takala
Kirsten E Lyke
Christopher V Plowe
Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
PLoS ONE
title Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
title_full Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
title_fullStr Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
title_full_unstemmed Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
title_short Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
title_sort safety and immunogenicity of an ama 1 malaria vaccine in malian adults results of a phase 1 randomized controlled trial
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001465&type=printable
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