http://dx.doi.org/10.1371/journal.pone.0005254
pubmed: 19390585
scopus: 65449181983
Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-l) administered in adjuvant system AS01B or AS02A
2009-04-23
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Background: This Phase 1/2a study evaluated the safety, immunogenicity, and efficacy of an experimental malaria vaccine comprised of the recombinant Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the 3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems. Methodology/Principal Findings: After a preliminary safety evaluation of low dose AMA-1/AS01B (10 μg/0.5 mL) in 5 adults, 30 malaria-naïve adults were randomly allocated to receive full dose (50 μg/0.5 mL) of AMA-1/AS01B (n = 15) or AMA-1/AS02A (n = 15), followed by a malaria challenge. All vaccinations were administered intramuscularly on a 0-, 1-, 2-month schedule. All volunteers experienced transient injection site erythema, swelling and pain. Two weeks post-third vaccination, anti-AMA-1 Geometric Mean Antibody Concentrations (GMCs) with 95% Confidence Intervals (CIs) were high: low dose AMA-1/AS01B 196 μg/mL (103-371 μg/mL), full dose AMA-1/AS01B 279 μg/mL (210-369 μg/ mL) and full dose AMA-1/AS02A 216 μg/mL (169-276 μg/mL) with no significant difference among the 3 groups. The three vaccine formulations elicited equivalent functional antibody responses, as measured by growth inhibition assay (GIA), against homologous but not against heterologous (FVO) parasites as well as demonstrable interferon-gamma (IFN-γ) responses. To assess efficacy, volunteers were challenged with P. falciparum-infected mosquitoes, and all became parasitemic, with no significant difference in the prepatent period by either light microscopy or quantitative polymerase chain reaction (qPCR). However, a small but significant reduction of parasitemia in the AMA-1/AS02A group was seen with a statistical model employing qPCR measurements. Significance: All three vaccine formulations were found to be safe and highly immunogenic. These immune responses did not translate into significant vaccine efficacy in malaria-naïve adults employing a primary sporozoite challenge model, but encouragingly, estimation of parasite growth rates from qPCR data may suggest a partial biological effect of the vaccine. Further evaluation of the immunogenicity and efficacy of the AMA-1/AS02A formulation is ongoing in a malaria-experienced pediatric population in Mali.
- adult
- article
- female
- human
- male
- metabolism
- middle aged
- major clinical study
- controlled study
- clinical trial
- controlled clinical trial
- drug dose comparison
- genetics
- randomized controlled trial
- animal
- immunogenicity
- immunology
- adolescent
- double blind procedure
- fatigue
- drug efficacy
- liposome
- drug megadose
- myalgia
- nausea
- low drug dose
- allele
- enzyme linked immunosorbent assay
- gamma interferon
- drug combination
- membrane protein
- phase 2 clinical trial
- arthralgia
- drug safety
- drug eruption
- drug derivative
- antibody detection
- immunological adjuvant
- pruritus
- drug induced headache
- malaise
- phase 1 clinical trial
- ASO2A adjuvant
- Plasmodium falciparum
- Plasmodium
- antibody response
- apical membrane antigen 1
- chloroquine
- apical membrane antigen I
- drug fever
- injection site erythema
- injection site swelling
- injection site pain
- lipid A
- malaria falciparum
- malaria vaccine
- papule
- parasite antibody
- parasitemia
- protozoal protein
- saponin
- skin inflammation
- parasite antigen
- sporozoite
- vaccine
- volunteer
- dose ama -1/as
- malaria
- study
- group
- immunization
- phase
- falciparum
- antigen
- trial
- parasite
- blood
- antibody
- efficacy
- challenge
- response
- control
- plasmodium
- malaria-na ıve adults
