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


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov NCT00358332 [NCT00358332].
Malaria Research and Training Center, University of Bamako, Bamako, Mali.
Mahamadou A
MA
Thera
Ogobara K
OK
Doumbo
Drissa
D
Coulibaly
Matthew B
MB
Laurens
Abdoulaye K
AK
Kone
Ando B
AB
Guindo
Karim
K
Traore
Mady
M
Sissoko
Dapa A
DA
Diallo
Issa
I
Diarra
Bourema
B
Kouriba
Modibo
M
Daou
Amagana
A
Dolo
Mounirou
M
Baby
Mahamadou S
MS
Sissoko
Issaka
I
Sagara
Amadou
A
Niangaly
Idrissa
I
Traore
Ally
A
Olotu
Olivier
O
Godeaux
Amanda
A
Leach
Marie-Claude
MC
Dubois
W Ripley
WR
Ballou
Joe
J
Cohen
Darby
D
Thompson
Tina
T
Dube
Lorraine
L
Soisson
Carter L
CL
Diggs
Shannon L
SL
Takala
Kirsten E
KE
Lyke
Brent
B
House
David E
DE
Lanar
Sheetij
S
Dutta
D Gray
DG
Heppner
Christopher V
CV
Plowe
D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007114:Immunization / Q000009:adverse effects / Q000379:methods; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008302:Mali; D008565:Membrane Proteins / Q000276:immunology*; D010146:Pain / Q000209:etiology; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D014839:Vomiting / Q000209:etiology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium