Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Malaria Vaccine Development Branch (MVDB), National Institute of Allergy and Infectious Disease, National Institutes of Health (NIAID/NIH), Rockville, MD, United States.
Vaccine. 2010 Mar 2;28(10):2236-2242. doi: 10.1016/j.vaccine.2009.12.049. Epub 2010 Jan 4.
A Phase 1 trial was conducted in malaria-naïve adults to evaluate the recombinant protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1) formulated in Montanide 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 microg protein at 0 and 3 months and four subjects were enrolled and received one vaccination of 80 microg 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 1 or 2 local reactions. All related systemic reactogenicity was grade 1 or 2, except one instance of grade 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 microg group compared to the 5 microg 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-naïve Australian adults. It is reasonably tolerated, though some transient, severe, and late local reactions are seen.
一项在无疟疾史的成年人中进行的 1 期临床试验，旨在评估重组蛋白疫苗顶膜蛋白 1-组合 1（AMA1-C1），该疫苗以 Montanide ISA 720（SEPPIC，法国）为佐剂配制而成，这是一种水包油佐剂。由于与稳定性或效力无关的配方问题，疫苗接种提前停止。24 名受试者（每组 12 名）入组并在 0 月和 3 月接受 5 或 20μg 蛋白接种，4 名受试者入组并接受 80μg 蛋白一次接种。首次接种后，几乎所有受试者均出现轻度至中度局部反应，6 名受试者出现延迟性局部反应，发生在第 9 天或之后。第二次接种后，3 名受试者出现短暂的 3 级（严重）局部反应；其余受试者出现 1 级或 2 级局部反应。所有相关的全身不良反应均为 1 级或 2 级，仅有 1 例 3 级不适。抗 AMA1-C1 抗体反应呈剂量依赖性，且在每次接种后均可观察到，在大多数时间点，20μg 组的平均抗体水平比 5μg 组高 2-3 倍。体外生长抑制活性是抗 AMA1 抗体滴度的函数。以 ISA 720 配制的 AMA1-C1 在无疟疾史的澳大利亚成年人中具有免疫原性。它具有合理的耐受性，尽管有些是短暂的、严重的和迟发性的局部反应。
