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].
Thera
Mahamadou A
MA
Malaria Research and Training Center, University of Bamako, Bamako, Mali.
Doumbo
Ogobara K
OK
Coulibaly
Drissa
D
Laurens
Matthew B
MB
Kone
Abdoulaye K
AK
Guindo
Ando B
AB
Traore
Karim
K
Sissoko
Mady
M
Diallo
Dapa A
DA
Diarra
Issa
I
Kouriba
Bourema
B
Daou
Modibo
M
Dolo
Amagana
A
Baby
Mounirou
M
Sissoko
Mahamadou S
MS
Sagara
Issaka
I
Niangaly
Amadou
A
Traore
Idrissa
I
Olotu
Ally
A
Godeaux
Olivier
O
Leach
Amanda
A
Dubois
Marie-Claude
MC
Ballou
W Ripley
WR
Cohen
Joe
J
Thompson
Darby
D
Dube
Tina
T
Soisson
Lorraine
L
Diggs
Carter L
CL
Takala
Shannon L
SL
Lyke
Kirsten E
KE
House
Brent
B
Lanar
David E
DE
Dutta
Sheetij
S
Heppner
D Gray
DG
Plowe
Christopher V
CV
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