Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Vaccine. 2013 Jun 24;31(29):3025-33. doi: 10.1016/j.vaccine.2013.04.050. Epub 2013 May 9.
Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE(®) (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses.
Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination.
The primary endpoint of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0+7, Group: 0+28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0+7, Group: 0+28, and Group: 0, respectively (Chi-square test, P=0.77). Based on BN's Plaque Reduction Assay GMTs, Group: 0+7 was non-inferior to Group: 0+28 at Day 4, 180, and 365 after the second vaccination. On Day 14, Group: 0+7 and Group: 0+28 GMT were 10.8 (CI: 9.0, 12.9) and 30.2 (CI: 22.1, 41.1), respectively. Based on BN's Enzyme-linked immunosorbent assay, the proportion of subjects with positive titers for Group: 0+28 was significantly greater than that for Group: 0+7 after second vaccination at Days 4 and 180. By Day 14 after the second dose, the IFN-γ enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0+28 and Group: 0+7.
Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 10(8) TCID/mL) administered subcutaneously was safe and well tolerated. A second dose of IMVAMUNE at Day 28 compared to Day 7 provided greater antibody responses and the maximal number of responders. By Day 14 after the second dose, IFN-γ ELISPOT responses were similar for Group: 0+28 and Group: 0+7.
天花作为生物恐怖主义的制剂重新出现仍然令人担忧。通过评估免疫反应的幅度和动力学，比较了巴伐利亚北欧公司（BN）的 IMVAMUNE（®）（针对天花的改良安卡拉痘苗）缩短的给药方案与目前推荐的 0 天和 28 天方案的非劣效性。
将受试者分配接受皮下 IMVAMUNE 或安慰剂，在第 0 天和第 7 天、第 0 天和第 28 天或第 0 天。采集血液用于抗体和细胞介导的免疫检测。在最后一次接种疫苗后 12 个月内对受试者进行安全性随访。
本研究的主要终点是最后一次接种后 14 天的几何平均抗体滴度（GMT）。在 208 名入组的受试者中，191 名接受了疫苗（组：0+7、组：0+28 和组：0），17 名接受了安慰剂。第 0+7 组、第 0+28 组和第 0 组的受试者分别有 31.1%、25.4%和 28.6%报告中度/重度全身反应（卡方检验，P=0.77）。基于 BN 的蚀斑减少测定 GMT，第 0+7 组在第二次接种后第 4、180 和 365 天与第 0+28 组相当。在第 14 天，第 0+7 组和第 0+28 组的 GMT 分别为 10.8（CI：9.0，12.9）和 30.2（CI：22.1，41.1）。基于 BN 的酶联免疫吸附试验，第二次接种后第 4 天和第 180 天，第 0+28 组的阳性滴度比例明显大于第 0+7 组。在第二次接种后第 14 天，第 0+28 组和第 0+7 组的 IFN-γ 酶联免疫斑点（ELISPOT）反应相似。
总的来说，皮下给予标准剂量的 IMVAMUNE（0.5 mL 为 1 x 10（8）TCID/mL）是安全且耐受良好的。与第 7 天相比，第 28 天给予第二剂 IMVAMUNE 可提供更大的抗体反应和最大数量的应答者。在第二次接种后第 14 天，第 0+28 组和第 0+7 组的 IFN-γ ELISPOT 反应相似。
