TY - JOUR
T1 - Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-l) administered in adjuvant system AS01B or AS02A
AU - Spring, Michele D.
AU - Cummings, James F.
AU - Ockenhouse, Christian F.
AU - Dutta, Sheetij
AU - Reidler, Randall
AU - Angov, Evelina
AU - Bergmann-Leitner, Elke
AU - Stewart, V. Ann
AU - Bittner, Stacey
AU - Juompan, Laure
AU - Kortepeter, Mark G.
AU - Nielsen, Robin
AU - Krzych, Urszula
AU - Tierney, Ev
AU - Ware, Lisa A.
AU - Dowler, Megan
AU - Hermsen, Cornelus C.
AU - Sauerwein, Robert W.
AU - de Vlas, Sake J.
AU - Ofori-Anyinam, Opokua
AU - Lanar, David E.
AU - Williams, Jack L.
AU - Kester, Kent E.
AU - Tucker, Kathryn
AU - Shi, Meng
AU - Malkin, Elissa
AU - Long, Carole
AU - Diggs, Carter L.
AU - Soisson, Lorraine
AU - Duboiss, Marie Claude
AU - Ballou, W. Ripley
AU - Cohen, Joe
AU - Heppner, D. Gray
PY - 2009/4/23
Y1 - 2009/4/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=65449181983&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0005254
DO - 10.1371/journal.pone.0005254
M3 - Article
C2 - 19390585
AN - SCOPUS:65449181983
SN - 1932-6203
VL - 4
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e5254
ER -