Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children
Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children
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DOI：
10.1016/j.vaccine.2013.09.046
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发表时间：
2013-11-19
期刊：
影响因子：
5.5
通讯作者：
Schmidt, Alexander C.
中科院分区：
文献类型：
--
作者：
Englund, Janet A.;Karron, Ruth A.;Schmidt, Alexander C.
背景：人副流感病毒3型（HPIV 3）是婴幼儿上呼吸道和下呼吸道疾病的常见病因。在婴儿中评估了减毒活冷适应HPIV 3疫苗，但第二剂疫苗给药的合适间隔尚未defined.Methods：在盲法研究中，将年龄在6至36个月之间的HPIV 3血清阴性儿童以2：1的比例随机接受两剂10（5）TCID 50（50%组织培养感染剂量）的减毒活重组冷传代人PIV 3疫苗（rHPIV 3cp 45）或安慰剂，间隔6个月。在每次给药前和给药后约4-6周评估血清抗体水平。疫苗病毒感染性，定义为检测到的疫苗-HPIV 3在鼻洗液和/或血清抗体滴度的一个>= 4倍的上升，和reactogenicity进行了评估，在第3天，第7天，和14后immunity.Results：40 HPIV 3-血清阴性儿童（中位年龄13个月，范围6-35个月）入组; 27（68%）接受疫苗和13（32%）接受安慰剂。第1剂接种后，26例可评价疫苗接种者中有25例（96%）检测到免疫力，第2剂接种后，26例受试者中有9例（35%）检测到免疫力。在排毒的受试者中，第1次给药后病毒排毒的中位持续时间为12天（范围6-15天），第2次给药后为6天（范围3-8天），第1次给药后的平均峰值log（10）病毒滴度为3.4 PFU/mL（SD：1.0），而第2次给药后为1.5 PFU/mL（SD：0.92）。总体而言，反应原性是温和的，与疫苗和安慰剂组之间的发热和上呼吸道感染症状的比率没有差异。结论：rHPIV 3cp 45是免疫原性和良好的耐受性，在血清阴性的幼儿。在初次接种疫苗6个月后接种第二剂疫苗仅限于先前感染疫苗病毒的儿童;然而，第二剂疫苗在两名先前未感染的儿童中增强了抗体应答并诱导了抗体应答。(C)2013爱思唯尔有限公司保留所有权利。
Background: Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined.Methods: HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10(5) TCID50 (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a >= 4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization.Results: Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log(10) viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups.Conclusion: rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. (C) 2013 Elsevier Ltd. All rights reserved.