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

Michele D Spring, James F Cummings, Christian F Ockenhouse, Sheetij Dutta, Randall Reidler, Evelina Angov, Elke Bergmann-Leitner, V Ann Stewart, Stacey Bittner, Laure Juompan, Mark G Kortepeter, Robin Nielsen, Urszula Krzych, Ev Tierney, Lisa A Ware, Megan Dowler, Cornelus C Hermsen, Robert W Sauerwein, Sake J de Vlas, Opokua Ofori-Anyinam, David E Lanar, Jack L Williams, Kent E Kester, Kathryn Tucker, Meng Shi, Elissa Malkin, Carole Long, Carter L Diggs, Lorraine Soisson, Marie-Claude Dubois, W Ripley Ballou, Joe Cohen and D Gray Heppner

PLOS ONE, 2009, vol. 4, issue 4, 1-13

Abstract: 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. Trial Registration: www.clinicaltrials.gov NCT00385047

Date: 2009
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0005254

DOI: 10.1371/journal.pone.0005254

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