Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Virology. 2010 Apr 10;399(2):290-8. doi: 10.1016/j.virol.2010.01.015. Epub 2010 Feb 2.
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.
我们之前使用人类副流感病毒 3 型（HPIV3）作为载体来表达埃博拉病毒（EBOV）的 GP 糖蛋白。由此产生的 HPIV3/EboGP 疫苗在非人类灵长类动物模型中具有免疫原性和针对 EBOV 挑战的保护作用。然而，由于对 HPIV3 的预先存在的免疫力，该疫苗在成年人中是否有效仍不清楚。在这里，我们比较了 HPIV3 初免和 HPIV3 免疫恒河猴中 HPIV3/EboGP 的免疫原性。在单次剂量的 HPIV3/EboGP 后，与 HPIV3 初免动物相比，EBOV 特异性血清 ELISA 或中和抗体的滴度在 HPIV3 免疫动物中明显较低。然而，在两次剂量后，先前确定这两次剂量可完全预防 EBOV 挑战，两组之间的抗体滴度就无法区分。尽管存在预先存在的免疫力，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 HPIV3 重新感染的已知能力，也可能反映了载体病毒粒子中存在 EBOV GP，这使其对 HPIV3 特异性抗体的中和具有体外抗性。这些数据表明，HPIV3/EboGP 在成人和儿童中都将具有免疫原性。
