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Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: A phase 1 double blind randomized controlled dose escalation trial was conducted...

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Autores principales: Thera, Mahamadou A., Doumbo, Ogobara K., Coulibaly, Drissa, Diallo, Dapa A., Kone, Abdoulaye K., Guindo, Ando B., Traore, Karim, Dicko, Alassane, Sagara, Issaka, Sissoko, Mahamadou S., Baby, Mounirou, Sissoko, Mady, Diarra, Issa, Niangaly, Amadou, Dolo, Amagana, Daou, Modibo, Diawara, Sory I., Heppner, D. Gray, Stewart, V. Ann, Angov, Evelina, Bergmann-Leitner, Elke S., Lanar, David E., Dutta, Sheetij, Soisson, Lorraine, Diggs, Carter L., Leach, Amanda, Owusu, Alex, Dubois, Marie-Claude, Cohen, Joe, Nixon, Jason N., Gregson, Aric, Takala, Shannon L., Lyke, Kirsten E., Plowe, Christopher V.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2186380/
https://www.ncbi.nlm.nih.gov/pubmed/18213374
http://dx.doi.org/10.1371/journal.pone.0001465
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author Thera, Mahamadou A.
Doumbo, Ogobara K.
Coulibaly, Drissa
Diallo, Dapa A.
Kone, Abdoulaye K.
Guindo, Ando B.
Traore, Karim
Dicko, Alassane
Sagara, Issaka
Sissoko, Mahamadou S.
Baby, Mounirou
Sissoko, Mady
Diarra, Issa
Niangaly, Amadou
Dolo, Amagana
Daou, Modibo
Diawara, Sory I.
Heppner, D. Gray
Stewart, V. Ann
Angov, Evelina
Bergmann-Leitner, Elke S.
Lanar, David E.
Dutta, Sheetij
Soisson, Lorraine
Diggs, Carter L.
Leach, Amanda
Owusu, Alex
Dubois, Marie-Claude
Cohen, Joe
Nixon, Jason N.
Gregson, Aric
Takala, Shannon L.
Lyke, Kirsten E.
Plowe, Christopher V.
author_facet Thera, Mahamadou A.
Doumbo, Ogobara K.
Coulibaly, Drissa
Diallo, Dapa A.
Kone, Abdoulaye K.
Guindo, Ando B.
Traore, Karim
Dicko, Alassane
Sagara, Issaka
Sissoko, Mahamadou S.
Baby, Mounirou
Sissoko, Mady
Diarra, Issa
Niangaly, Amadou
Dolo, Amagana
Daou, Modibo
Diawara, Sory I.
Heppner, D. Gray
Stewart, V. Ann
Angov, Evelina
Bergmann-Leitner, Elke S.
Lanar, David E.
Dutta, Sheetij
Soisson, Lorraine
Diggs, Carter L.
Leach, Amanda
Owusu, Alex
Dubois, Marie-Claude
Cohen, Joe
Nixon, Jason N.
Gregson, Aric
Takala, Shannon L.
Lyke, Kirsten E.
Plowe, Christopher V.
author_sort Thera, Mahamadou A.
collection PubMed
description BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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 µg/AS02A 0.25 mL or FMP2.1 50 µg/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. CONCLUSION/SIGNIFICANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00308061
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spelling pubmed-21863802008-01-23 Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial Thera, Mahamadou A. Doumbo, Ogobara K. Coulibaly, Drissa Diallo, Dapa A. Kone, Abdoulaye K. Guindo, Ando B. Traore, Karim Dicko, Alassane Sagara, Issaka Sissoko, Mahamadou S. Baby, Mounirou Sissoko, Mady Diarra, Issa Niangaly, Amadou Dolo, Amagana Daou, Modibo Diawara, Sory I. Heppner, D. Gray Stewart, V. Ann Angov, Evelina Bergmann-Leitner, Elke S. Lanar, David E. Dutta, Sheetij Soisson, Lorraine Diggs, Carter L. Leach, Amanda Owusu, Alex Dubois, Marie-Claude Cohen, Joe Nixon, Jason N. Gregson, Aric Takala, Shannon L. Lyke, Kirsten E. Plowe, Christopher V. PLoS One Research Article BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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 µg/AS02A 0.25 mL or FMP2.1 50 µg/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. CONCLUSION/SIGNIFICANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00308061 Public Library of Science 2008-01-23 /pmc/articles/PMC2186380/ /pubmed/18213374 http://dx.doi.org/10.1371/journal.pone.0001465 Text en 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. 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
Thera, Mahamadou A.
Doumbo, Ogobara K.
Coulibaly, Drissa
Diallo, Dapa A.
Kone, Abdoulaye K.
Guindo, Ando B.
Traore, Karim
Dicko, Alassane
Sagara, Issaka
Sissoko, Mahamadou S.
Baby, Mounirou
Sissoko, Mady
Diarra, Issa
Niangaly, Amadou
Dolo, Amagana
Daou, Modibo
Diawara, Sory I.
Heppner, D. Gray
Stewart, V. Ann
Angov, Evelina
Bergmann-Leitner, Elke S.
Lanar, David E.
Dutta, Sheetij
Soisson, Lorraine
Diggs, Carter L.
Leach, Amanda
Owusu, Alex
Dubois, Marie-Claude
Cohen, Joe
Nixon, Jason N.
Gregson, Aric
Takala, Shannon L.
Lyke, Kirsten E.
Plowe, Christopher V.
Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2186380/
https://www.ncbi.nlm.nih.gov/pubmed/18213374
http://dx.doi.org/10.1371/journal.pone.0001465
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