A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial
A Dose-Escalation Safety and Immunogenicity Study of Live Attenuated Oral Rotavirus Vaccine 116E in Infants: A Randomized, Double-Blind, Placebo-Controlled Trial
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DOI：
10.1086/600104
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发表时间：
2009-08-01
影响因子：
6.4
通讯作者：
Vrati, Sudhanshu
中科院分区：
文献类型：
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作者：
Bhandari, Nita;Sharma, Pooja;Vrati, Sudhanshu
背景轮状病毒感染每年在印度儿童中造成122，000人死亡。新生儿轮状病毒候选疫苗116 E在印度进行了一项双盲、安慰剂对照剂量递增试验。评价了两个剂量的Vero细胞适应性疫苗。187名婴儿接受了1 × 10（4）个病灶形成单位（ffu）的疫苗剂量，182名婴儿接受了1 × 10（5）个病灶形成单位（ffu）的疫苗剂量，与安慰剂接受者按1：1随机分组。婴儿分别在8周、12周和16周接种疫苗，与常规疫苗分开。在疫苗和安慰剂接受者之间没有观察到临床不良事件或实验室毒性的显著差异。未发生与疫苗相关的严重不良事件。在首次接种1 × 10（4）ffu和1 × 10（5）ffu后，分别有66.7%和64.5%的婴儿轮状病毒免疫球蛋白A滴度增加4倍;在3次接种1 × 10（4）ffu和1 × 10（5）ffu后，分别有62.1%和89.7%的婴儿轮状病毒免疫球蛋白A滴度增加4倍;这些组与安慰剂组之间的差异具有统计学意义。接种三次1 × 10（4）ffu和1 × 10（5）ffu的疫苗剂量是安全的。1 × 10（5）-ffu剂量的116 E在3次给药后显示出稳健的免疫应答。这些有利的结果保证了候选疫苗的进一步开发，并为发展中国家的婴儿接种疫苗将预防轮状病毒感染的严重后遗症提供了乐观。
Background. Rotavirus infections cause similar to 122,000 deaths among Indian children annually.Methods. The neonatal rotavirus candidate vaccine 116E was tested in a double-blind, placebo-controlled dose-escalation trial in India. Two doses of the Vero cell-adapted vaccine were evaluated. One hundred eighty-seven infants received a vaccine dose of 1 X 10(4) focus-forming units (ffu) and 182 received a dose of 1 X 10(5) ffu in a 1:1 randomization with placebo recipients. Infants received the vaccine at 8, 12, and 16 weeks, separately from routine vaccines.Results. No significant differences in clinical adverse events or laboratory toxicity were observed between vaccine and placebo recipients. There were no vaccine-related serious adverse events. A 4-fold increase in rotavirus immunoglobulin A titer was observed in 66.7% and 64.5% of infants after the first administration and in 62.1% and 89.7% of infants after 3 administrations of doses of 1 X 10(4) ffu and 1 X 10(5) ffu, respectively; the differences between these groups and placebo recipients were statistically significant.Conclusions. Three administrations of vaccine doses of 1 X 10(4) ffu and 1 X 10(5) ffu were safe. The 1 X 10(5)-ffu dose of 116E demonstrated a robust immune response after 3 administrations. These favorable results warrant further development of the vaccine candidate and provide optimism that vaccinating infants in the developing world will prevent serious sequelae of rotavirus infection.