TY - JOUR
T1 - Extended safety, immunogenicity and efficacy of a blood-stage malaria vaccine in Malian children
T2 - 24-Month follow-up of a randomized, double-blinded phase 2 trial
AU - Laurens, Matthew B.
AU - Thera, Mahamadou A.
AU - Coulibaly, Drissa
AU - Ouattara, Amed
AU - Kone, Abdoulaye K.
AU - Guindo, Ando B.
AU - Traore, Karim
AU - Traore, Idrissa
AU - Kouriba, Bourema
AU - Diallo, Dapa A.
AU - Diarra, Issa
AU - Daou, Modibo
AU - Dolo, Amagana
AU - Tolo, Youssouf
AU - Sissoko, Mahamadou S.
AU - Niangaly, Amadou
AU - Sissoko, Mady
AU - Takala-Harrison, Shannon
AU - Lyke, Kirsten E.
AU - Wu, Yukun
AU - Blackwelder, William C.
AU - Godeaux, Olivier
AU - Vekemans, Johan
AU - Dubois, Marie Claude
AU - Ballou, W. Ripley
AU - Cohen, Joe
AU - Dube, Tina
AU - Soisson, Lorraine
AU - Diggs, Carter L.
AU - House, Brent
AU - Bennett, Jason W.
AU - Lanar, David E.
AU - Dutta, Sheetij
AU - Heppner, D. Gray
AU - Plowe, Christopher V.
AU - Doumbo, Ogobara K.
PY - 2013/11/18
Y1 - 2013/11/18
N2 - Background: The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allelespecific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods: A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02 A was conducted in Bandiagara, Mali. Children aged 1-6 years were randomized in a 1:1 ratio to receive FMP2.1/AS02 A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings: 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation: Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season. Trial Registration: Clinicaltrials.gov NCT00460525.
AB - Background: The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allelespecific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods: A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02 A was conducted in Bandiagara, Mali. Children aged 1-6 years were randomized in a 1:1 ratio to receive FMP2.1/AS02 A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings: 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation: Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during the second malaria season. Trial Registration: Clinicaltrials.gov NCT00460525.
UR - http://www.scopus.com/inward/record.url?scp=84894187377&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0079323
DO - 10.1371/journal.pone.0079323
M3 - Article
C2 - 24260195
AN - SCOPUS:84894187377
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e79323
ER -