Bharat Biotech International Limited, Hyderabad, Telangana, India.
Centre for Vaccine Development, University of Maryland School of Medicine, Baltimore.
Clin Infect Dis. 2015 Aug 1;61(3):393-402. doi: 10.1093/cid/civ295. Epub 2015 Apr 13.
Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age.
Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion [SCN]) 42 days after immunization.
Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95% CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI], 60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed.
Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups.
CTRI/2011/08/001957, CTRI/2014/01/004341.
伤寒沙门氏菌引起的伤寒在发展中国家仍是一个主要的公共卫生问题。Typbar-TCV 是一种用于 6 个月以上人群的伤寒 Vi 多糖-破伤风类毒素结合疫苗。
654 名 2-45 岁的健康受试者参加了一项双盲、随机对照试验（RCT），他们接受了一剂 Typbar-TCV 或对照“Vi 多糖”（Typbar）的治疗，327 名 6-23 个月的健康受试者参加了一项开放性标签试验（OLT），他们接受了一剂 Typbar-TCV 的治疗；两组均接受了来自不同批次的单剂或多剂治疗。2 年后，每组的部分受试者接受了加强剂量。主要目标包括分析免疫后 42 天（血清转化率[SCN]）血清抗-Vi 免疫球蛋白 G（IgG）酶联免疫吸附试验滴度的几何平均滴度（GMT）和 4 倍升高。
RCT 中的 Typbar-TCV 组受试者在免疫后 42 天（SCN，97%；GMT，1293[95%置信区间{CI}，1153-1449]）比接受 Typbar 的受试者（SCN，93%；GMT，411[95%CI，359-471]）（P<.001）获得了更高的抗-Vi IgG GMT。OLT 中的 Typbar-TCV 高度免疫原性（SCN，98%；GMT，1937[95%CI，1785-2103]）。接种疫苗 2 年后，Typbar-TCV 组的抗-Vi 滴度仍较高（GMT，82[95%CI，73-92]）；与 RCT 中接受 Typbar 的受试者（GMT，46[95%CI，40-53]；GMAI 46%）相比，表现出更高的亲和力（几何平均亲和力指数[GMAI]，60%）（P<.001）。OLT Typbar-TCV 组受试者的 GMT 为 48（95%CI，42-55），GMAI 为 57%。Typbar-TCV 诱导了所有年龄段的多种 IgG 亚类和强烈的加强反应。未观察到与疫苗相关的严重不良事件。
单剂 Typbar-TCV 具有良好的耐受性，可在各年龄段诱导持久的血清抗-Vi IgG。
CTRI/2011/08/001957，CTRI/2014/01/004341。
