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.


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/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.


CONCLUSIONS
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.
Thera
Mahamadou A
MA
Malaria Research and Training Center, University of Bamako, Bamako, Mali.
Doumbo
Ogobara K
OK
Coulibaly
Drissa
D
Diallo
Dapa A
DA
Kone
Abdoulaye K
AK
Guindo
Ando B
AB
Traore
Karim
K
Dicko
Alassane
A
Sagara
Issaka
I
Sissoko
Mahamadou S
MS
Baby
Mounirou
M
Sissoko
Mady
M
Diarra
Issa
I
Niangaly
Amadou
A
Dolo
Amagana
A
Daou
Modibo
M
Diawara
Sory I
SI
Heppner
D Gray
DG
Stewart
V Ann
VA
Angov
Evelina
E
Bergmann-Leitner
Elke S
ES
Lanar
David E
DE
Dutta
Sheetij
S
Soisson
Lorraine
L
Diggs
Carter L
CL
Leach
Amanda
A
Owusu
Alex
A
Dubois
Marie-Claude
MC
Cohen
Joe
J
Nixon
Jason N
JN
Gregson
Aric
A
Takala
Shannon L
SL
Lyke
Kirsten E
KE
Plowe
Christopher V
CV
D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D016778:Malaria, Falciparum / Q000517:prevention & control; D008297:Male; D008302:Mali; D008565:Membrane Proteins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium