Accession Number:

ADA513498

Title:

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

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Report Date:

2009-04-01

Pagination or Media Count:

14.0

Abstract:

This Phase 12a 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. MethodologyPrincipal Findings After a preliminary safety evaluation of low-dose AMA-1AS01B 10 mg0.5 mL in 5 adults, 30 malaria-naive adults were randomly allocated to receive full dose 50 mg0.5 mL of AMA-1AS01B n 15 or AMA-1AS02A 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-1AS01B 196 mgmL 103-371 mgmL, full-dose AMA-1AS01B 279 mgmL 210-369 mgmL and full-dose AMA-1AS02A 216 mgmL 169-276 mgmL 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-gamma 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-1AS02A group was seen with a statistical model employing qPCR measurements.

Subject Categories:

  • Medicine and Medical Research
  • Microbiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE