世界卫生组织建议将轮状病毒疫苗纳入所有国家免疫计划。一些目前获得许可的口服轮状病毒疫苗含有缓冲剂(作为即用型液体制剂的一部分或在重建过程中添加),以减少疫苗病毒在婴儿肠道中的可能降解,这在疫苗给药过程中提出了一些程序性挑战(大剂量或重组要求)。因为ROTAVAC®,世卫组织预先认证的疫苗,来自116E新生儿菌株,我们评估了不含缓冲液的ROTAVAC®和含缓冲液的ROTAVAC®的免疫原性和安全性,单盲,印度健康婴儿的随机临床试验。
900名婴儿,大约6、10和14周龄,被分配到3组,分别口服ROTAVAC®(0.5mL剂量):(i)在施用ROTAVAC®前5分钟使用2.5mL柠檬酸盐-碳酸氢盐缓冲液(I组),(ii)ROTAVAC®,独自一人,没有任何缓冲液(第二组),或(iii)ROTAVAC®,在施用前立即与缓冲液混合(组III)。比较了各组之间的非劣性血清学反应(通过血清抗轮状病毒IgA检测)和安全性的差异。
第84天(剂量3后28天)接种疫苗后的几何平均滴度为19.6(95CI:17.0,22.7),I组的20.7(95CI:17.9,24)和19.2(95CI:16.8,22.1),分别为II和III。Further,各组血清转换率和不良事件分布相似.
在没有缓冲剂的情况下以0.5mL剂量体积施用ROTAVAC®显示出良好的耐受性和免疫原性。鉴于菌株的同源性质,似乎ROTAVAC®复制良好并且即使不施用缓冲液也赋予免疫力。
The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration. Because ROTAVAC®, a WHO prequalified vaccine, was derived from the 116E neonatal strain, we evaluated the immunogenicity and safety of ROTAVAC® without buffer and ROTAVAC® with buffer in a phase 4, multicentre, single-blind, randomized clinical
trial in healthy infants in India.
900 infants, approximately 6, 10 and 14 weeks of age, were assigned to 3 groups to receive ROTAVAC® (0.5 mL dose) orally: (i) 2.5 mL of citrate-bicarbonate buffer 5 minutes prior to administration of ROTAVAC® (Group I), (ii) ROTAVAC®, alone, without any buffer (Group II), or (iii) ROTAVAC®, mixed with buffer immediately before administration (Group III). Non-inferiority was compared among the groups for differences in serological responses (detected by serum anti-rotavirus IgA) and safety.
Geometric mean titers post vaccination at day 84 (28 days after dose 3) were 19.6 (95%CI: 17.0, 22.7), 20.7 (95%CI: 17.9, 24) and 19.2 (95%CI: 16.8, 22.1) for groups I, II and III respectively. Further, seroconversion rates and distribution of adverse events were similar among groups.
Administration of ROTAVAC® at a 0.5 mL dose volume without buffering agent was shown to be well tolerated and immunogenic. Given the homologous nature of the strain, it is plausible that ROTAVAC® replicates well and confers immunity even without buffer administration.