疟疾初治成年人中含或不含 CPG 7909 的恶性疟原虫红内期疫苗 MSP1(42)-C1/Alhydrogel 的 1 期临床试验。
Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults.
机构信息
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Rockville, Maryland, USA.
出版信息
PLoS One. 2010 Jan 22;5(1):e8787. doi: 10.1371/journal.pone.0008787.
BACKGROUND
Merozoite surface protein 1(42) (MSP1(42)) is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42) were mixed (MSP1(42)-C1). To improve the level of antibody response, MSP1(42)-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909.
METHODS
A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42)-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months.
RESULTS
Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema) and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42) antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42)-C1/Alhydrogel alone (p<0.0001). After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10%) in the non CPG groups versus 14% (3 to 32%) in the CPG groups.
CONCLUSION/SIGNIFICANCE: The favorable safety profile and high antibody responses induced with MSP1(42)-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42)-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00320658.
背景
裂殖子表面蛋白 1(42)（MSP1(42)）是一种主要的血阶段疟疾疫苗候选物。为了诱导涵盖主要抗原多态性的免疫反应，FVO 和 3D7 重组 MSP1(42)蛋白被混合（MSP1(42)-C1）。为了提高抗体反应水平，MSP1(42)-C1 与 Alhydrogel 联合新型佐剂 CPG 7909 进行了配制。
方法
在华盛顿特区的免疫研究中心，对健康的无疟疾成年人进行了 1 期临床试验，以评估 MSP1(42)-C1/Alhydrogel +/-CPG 7909 的安全性和免疫原性。60 名志愿者按剂量递增队列入组，并随机接受三种疫苗接种，分别为 40 或 160μg 蛋白吸附于 Alhydrogel +/-560μgCPG 7909，在 0、1 和 2 个月时进行。
结果
疫苗接种耐受性良好，仅有 1 例与疫苗相关的不良事件为严重（3 级注射部位红斑），其余所有疫苗相关不良事件均为轻度或中度。接受 CPG 的组中，局部不良事件更频繁且更严重。与单独使用 MSP1(42)-C1/Alhydrogel 相比，CPG 的添加可使第二次免疫后两周时的抗-MSP1(42)抗体反应增加高达 49 倍，第三次免疫后两周时增加 8 倍（p<0.0001）。在第三次免疫后，通过体外生长抑制测定法测试了抗体的功能。抑制作用是抗体滴度的函数，非 CPG 组平均为 3%（范围为-2 至 10%），而 CPG 组为 14%（3 至 32%）。
结论/意义：MSP1(42)-C1/Alhydrogel +CPG 7909 诱导的良好安全性概况和高抗体反应令人鼓舞。MSP1(42)-C1/Alhydrogel 正在与其他血阶段抗原结合，并将与 CPG 7909 联合使用的佐剂进行联合。
试验注册
ClinicalTrials.gov 标识符：NCT00320658。
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