Safety and Immunogenicity of an Intranasal Sendai Virus-Based Human Parainfluenza Virus Type 1 Vaccine in 3-to 6-Year-Old Children

Safety and Immunogenicity of an Intranasal Sendai Virus-Based Human Parainfluenza Virus Type 1 Vaccine in 3-to 6-Year-Old Children
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DOI:
10.1128/cvi.00618-14
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发表时间:
2015-03-01
影响因子:
--
通讯作者:
Hurwitz, Julia L.
Hurwitz, Julia L.
中科院分区:
生物3区
文献类型:
--
作者:
Adderson, Elisabeth;Branum, Kristen;Hurwitz, Julia L.

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人类副流感病毒1型(hPIV-1)是喉气管支气管炎(Croup)的最常见原因,仅在美国每年就导致数万人住院。目前还没有获得许可的疫苗。我们已经开发出小鼠PIV-1(仙台病毒[SeV])作为针对hPIV-1的Jennerian活疫苗。在这里,我们描述了在剂量递增研究中对健康的3至6岁hPIV-1血清阳性儿童进行的疫苗测试。通过鼻腔给每个研究参与者一剂疫苗(5×10(5)、5×10(6)或5×10(7)50%鸡蛋感染剂量)。所有研究参与者对疫苗的耐受性都很好。在任何参与者的呼吸道中都没有疫苗病毒复制的迹象。大多数儿童在接种疫苗后4周内对hPIV-1的抗体结合和中和反应增加。在几名儿童中,在接种疫苗后至少6个月内,抗体反应保持在传入水平以上。数据表明,即使疫苗接受者由于以前接触hPIV-1而预先存在交叉反应抗体,SEV也可能为3至6岁的儿童提供好处。结果鼓励对血清阴性儿童进行SEV检测,以预防由hPIV-1感染引起的严重呼吸道疾病。
Human parainfluenza virus type 1 (hPIV-1) is the most common cause of laryngotracheobronchitis (croup), resulting in tens of thousands of hospitalizations each year in the United States alone. No licensed vaccine is yet available. We have developed murine PIV-1 (Sendai virus [SeV]) as a live Jennerian vaccine for hPIV-1. Here, we describe vaccine testing in healthy 3- to 6-year-old hPIV-1-sero-positive children in a dose escalation study. One dose of the vaccine (5 X 10(5), 5 X 10(6), or 5 X 10(7) 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3- to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections.