Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult Malians.
BACKGROUND
Apical Membrane Antigen 1 (AMA1) of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses.


RESULTS
A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax). Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort) and randomized 2:1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 microg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 microg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels.


CONCLUSIONS
Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum.


BACKGROUND
ClinicalTrials.gov NCT00343005.
Dicko
Alassane
A
Malaria Research and Training Center, Department of Hematology, University of Bamako, Bamako, Mali.
Diemert
David J
DJ
Sagara
Issaka
I
Sogoba
Moussa
M
Niambele
Mohamed B
MB
Assadou
Mahamadoun H
MH
Guindo
Ousmane
O
Kamate
Beh
B
Baby
Mounirou
M
Sissoko
Mady
M
Malkin
Elissa M
EM
Fay
Michael P
MP
Thera
Mahamadou A
MA
Miura
Kazutoyo
K
Dolo
Amagana
A
Diallo
Dapa A
DA
Mullen
Gregory E
GE
Long
Carole A
CA
Saul
Allan
A
Doumbo
Ogobara
O
Miller
Louis H
LH
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry*; D015331:Cohort Studies; D004311:Double-Blind Method; D006801:Humans; D017780:Malaria Vaccines / Q000737:chemistry*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008302:Mali; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D016896:Treatment Outcome
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D011994:Recombinant Proteins