Phase 1/2a Study of the Malaria Vaccine Candidate Apical Membrane Antigen-1 (AMA-1) Administered in Adjuvant System AS01B or AS02A

摘要

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 mg/0.5 mL) in 5 adults, 30 malaria-naive adults were randomly allocated to receive full dose (50 mg/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 mg/mL (103-371 mg/mL), full-dose AMA-1/AS01B 279 mg/mL (210-369 mg/mL) and full- dose AMA-1/AS02A 216 mg/mL (169-276 mg/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-&(number sign)61543;) 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.