Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults

TY - JOUR

T1 - Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage malaria vaccine AMA1-C1/ISA 720 in Australian adults

AU - Pierce, Mark A.

AU - Ellis, Ruth D.

AU - Martin, Laura B.

AU - Malkin, Elissa

AU - Tierney, Eveline

AU - Miura, Kazutoyo

AU - Fay, Michael P.

AU - Marjason, Joanne

AU - Elliott, Suzanne L.

AU - Mullen, Gregory

AU - Rausch, Kelly

AU - Zhu, Daming

AU - Long, Carole A.

AU - Miller, Louis H.

PY - 2010/3/2

Y1 - 2010/3/2

N2 - A Phase I trial was conducted in malaria-naive adults to evaluate the recombinant protein vaccine apical membrane antigen I -Combination 1 (AMA1-C1) formulated in Montanide (R) ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were halted early due to a formulation issue unrelated to stability or potency. Twenty-four subjects (12 in each group) were enrolled and received 5 or 20 mu g protein at 0 and 3 months and four subjects were enrolled and received one vaccination of 80 mu g protein. After first vaccination, nearly all subjects experienced mild to moderate local reactions and six experienced delayed local reactions occurring at Day 9 or later. After the second vaccination, three subjects experienced transient grade 3 (severe) local reactions; the remainder experienced grade I or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except one instance ofgrade 3 malaise. Anti-AMA1-C1 antibody responses were dose dependent and seen following each vaccination, with mean antibody levels 2-3 fold higher in the 20 mu g group compared to the 5 mu g group at most time points. In vitro growth-inhibitory activity was a function of the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in malaria-naive Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen. Published by Elsevier Ltd.

AB - A Phase I trial was conducted in malaria-naive adults to evaluate the recombinant protein vaccine apical membrane antigen I -Combination 1 (AMA1-C1) formulated in Montanide (R) ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were halted early due to a formulation issue unrelated to stability or potency. Twenty-four subjects (12 in each group) were enrolled and received 5 or 20 mu g protein at 0 and 3 months and four subjects were enrolled and received one vaccination of 80 mu g protein. After first vaccination, nearly all subjects experienced mild to moderate local reactions and six experienced delayed local reactions occurring at Day 9 or later. After the second vaccination, three subjects experienced transient grade 3 (severe) local reactions; the remainder experienced grade I or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except one instance ofgrade 3 malaise. Anti-AMA1-C1 antibody responses were dose dependent and seen following each vaccination, with mean antibody levels 2-3 fold higher in the 20 mu g group compared to the 5 mu g group at most time points. In vitro growth-inhibitory activity was a function of the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in malaria-naive Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen. Published by Elsevier Ltd.

U2 - 10.1016/j.vaccine.2009.12.049

DO - 10.1016/j.vaccine.2009.12.049

M3 - Article

SN - 1873-2518

VL - 28

SP - 2236

EP - 2242

JO - Vaccine

JF - Vaccine

IS - 10

ER -