Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens
Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens
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DOI：
10.1073/pnas.0703584104
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发表时间：
2007-06-05
影响因子：
11.1
通讯作者：
Bukreyev, Alexander
中科院分区：
文献类型：
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作者：
DiNapoli, Joshua M.;Kotelkin, Alexander;Bukreyev, Alexander
2002-2003年严重急性呼吸道综合征相关冠状病毒（SARS-CoV）在国际上的爆发突出表明，需要开发预先测试的人类疫苗载体，用于对新出现的病原体作出快速反应。我们评估了纽卡斯尔病病毒（NDV），一种在灵长类动物中高度减毒的禽副粘病毒，作为以SARS-CoV作为测试病原体的局部呼吸道疫苗载体。完整的重组NDV被设计成从添加的转录单位表达SARSCoV刺突S糖蛋白，病毒中和和主要保护性抗原。非洲绿色猴通过呼吸道接种两剂疫苗后，产生的SARS-CoV中和抗体滴度与用不同的实验性SARS-CoV疫苗免疫并用SARS-CoV攻击的动物中观察到的强烈二次应答相当。当用表达S的NDV免疫的动物用高剂量的SARS-CoV攻击时，在病毒复制高峰时通过尸检获得的肺组织的直接病毒测定表明，与对照动物相比，肺SARS-CoV滴度平均降低236倍或1，102倍（取决于NDV载体构建体）。NDV具有进一步开发为预测试的高度减毒的鼻内载体的潜力，以可用于加速针对人的疫苗开发，人通常缺乏针对NDV的预先存在的免疫力。
The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002-2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to express the SARSCoV spike S glycoprotein, the viral neutralization and major protective antigen, from an added transcriptional unit. African green monkeys immunized through the respiratory tract with two doses of the vaccine developed a titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary response observed in animals that have been immunized with a different experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals immunized with NDV expressing S were challenged with a high dose of SARS-CoV, direct viral assay of lung tissues taken by necropsy at the peak of viral replication demonstrated a 236- or 1,102-fold (depending on the NDV vector construct) mean reduction in pulmonary SARS-CoV titer compared with control animals. NDV has the potential for further development as a pretested, highly attenuated, intranasal vector to be available for expedited vaccine development for humans, who generally lack preexisting immunity against NDV.