Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic
Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic
复制标题
DOI：
10.1016/j.virol.2010.01.015
复制
发表时间：
2010-04-10
期刊：
影响因子：
3.7
通讯作者：
Collins, Peter L.
中科院分区：
文献类型：
--
作者：
Bukreyev, Alexander A.;DiNapoli, Joshua M.;Collins, Peter L.
我们以前使用人副流感病毒3型（HPIV3）作为载体表达埃博拉病毒（EBOV）GP糖蛋白。所得HPIV3/EboGP疫苗在非人灵长类动物模型中具有免疫原性和针对EBOV攻击的保护性。然而，由于对HPIV 3的预先存在的免疫力，该疫苗是否对成人有效仍不清楚。在此，在HPIV3未感染和HPIV3免疫恒河猴中比较HPIV3/EboGP的免疫原性。在单剂量的HPIV3/EboGP后，与HPIV3未感染动物相比，HPIV3免疫动物中EBOV特异性血清ELISA或中和抗体的滴度显著更低。然而，在先前确定为针对EBOV攻击的完全保护所需的两个剂量后，两组之间的抗体滴度不可区分。尽管预先存在免疫力，但疫苗病毒似乎在呼吸道中以降低的水平复制。这可能反映了已知的HPIV 3再感染能力，也可能反映了载体病毒粒子中存在EBOV GP，其赋予对HPIV 3特异性抗体体外中和的抗性。这些数据表明HPIV3/EboGP在成人和儿童中具有免疫原性。爱思唯尔公司出版
We previously used human parainfluenza virus type 3 (HPIV3) as a vector to express the Ebola virus (EBOV) GP glycoprotein. The resulting HPIV3/EboGP vaccine was immunogenic and protective against EBOV challenge in a non-human primate model. However, it remained unclear whether the vaccine would be effective in adults due to preexisting immunity to HPIV3. Here, the immunogenicity of HPIV3/EboGP was compared in HPIV3-naive and HPIV3-immune Rhesus monkeys. After a single dose of HPIV3/EboGP, the titers of EBOV-specific serum ELISA or neutralization antibodies were substantially less in HPIV3-immune animals compared to HPIV3-naive animals. However, after two doses, which were previously determined to be required for complete protection against EBOV challenge, the antibody titers were indistinguishable between the two groups. The vaccine virus appeared to replicate, at a reduced level, in the respiratory tract despite the preexisting immunity. This may reflect the known ability of HPIV3 to re-infect and may also reflect the presence of EBOV GP in the vector virion, which confers resistance to neutralization in vitro by HPIV3-specific antibodies. These data suggest that HPIV3/EboGP will be immunogenic in adults as well as children. Published by Elsevier Inc.