Phase 1 Study in Malaria Naïve Adults of BSAM2/Alhydrogel®+CPG 7909, a Blood Stage Vaccine against <em>P. falciparum</em> Malaria

A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP142, with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30) volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP142. Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. In vitro growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted. Trial RegistrationClinicaltrials.gov NCT00889616本研究在未感染过疟疾的成人中开展了1期剂量爬坡试验，以评估血期疟疾疫苗BSAM2/Alhydrogel®+ CPG 7909的安全性、反应原性及免疫原性。BSAM2为重组顶膜抗原1（AMA1）与裂殖子表面蛋白142（MSP142）的FVO及3D7等位基因的组合制剂，四种蛋白按等重量配比混合后吸附于Alhydrogel®佐剂，并辅以佐剂CPG 7909进行接种。本研究共纳入30名志愿者，分为两个剂量组：15名志愿者在第0、56、180天最多接种3剂总蛋白含量为40μg的疫苗，另外15名志愿者在相同接种周期内最多接种3剂总蛋白含量为160μg的疫苗。多数相关不良事件为轻度或中度，但有4名志愿者出现严重全身不良反应，另有2名志愿者因不良事件终止疫苗接种。采用高剂量制剂完成2剂接种后，志愿者体内的几何平均抗体水平分别为：AMA1达136μg/ml，MSP142达78μg/ml。高剂量组与低剂量组的抗体应答无显著差异，且第3剂接种后抗体水平未进一步升高。体外生长抑制试验结果呈阳性，且与抗AMA1抗体应答密切相关。目前一项针对疟疾暴露成人的1b期临床试验正在开展中。临床试验注册：ClinicalTrials.gov NCT00889616