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经舌下给予表达人呼吸道合胞病毒优化密码子可溶性融合糖蛋白的辅助依赖性腺病毒载体可在小鼠中引发保护性免疫。

Sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in mice.

机构信息

College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing 100044, China.

College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing 100044, China.

出版信息

Antiviral Res. 2014 May;105:72-9. doi: 10.1016/j.antiviral.2014.02.003. Epub 2014 Feb 19.

Abstract

Sublingual (s.l.) immunization has been described as a convenient and safe way to induce mucosal immune responses in the respiratory and genital tracts. We constructed a helper-dependent adenoviral (HDAd) vector expressing a condon-optimized soluble fusion glycoprotein (sFsyn) of respiratory syncytial virus (HDAd-sFsyn) and explored the potential of s.l. immunization with HDAd-sFsyn to stimulate immune responses in the respiratory mucosa. The RSV specific systemic and mucosal immune responses were generated in BALB/c mice, and the serum IgG with neutralizing activity was significantly elevated after homologous boost with s.l. application of HDAd-sFsyn. Humoral immune responses could be measured even 14weeks after a single immunization. Upon challenge, s.l. immunization with HDAd-sFsyn displayed an effective protection against RSV infection. These findings suggest that s.l. administration of HDAd-sFsyn acts as an effective and safe mucosal vaccine against RSV infection, and may be a useful tool in the prevention of RSV infection.

摘要

黏膜下(s.l.)免疫已被描述为一种在呼吸道和生殖道中诱导黏膜免疫应答的方便且安全的方法。我们构建了一种表达呼吸合胞病毒(RSV)的条件优化可溶性融合糖蛋白(sFsyn)的辅助依赖性腺病毒(HDAd)载体(HDAd-sFsyn),并探索了用 HDAd-sFsyn 经黏膜下免疫接种刺激呼吸道黏膜免疫应答的潜力。在 BALB/c 小鼠中产生了 RSV 特异性全身和黏膜免疫应答,并且同源加强后经 s.l.应用 HDAd-sFsyn 明显提高了血清 IgG 的中和活性。单次免疫接种后甚至 14 周仍可检测到体液免疫应答。在挑战中,HDAd-sFsyn 的 s.l.免疫接种显示出对 RSV 感染的有效保护作用。这些发现表明,HDAd-sFsyn 的 s.l.给药可作为针对 RSV 感染的有效且安全的黏膜疫苗,并且可能是预防 RSV 感染的有用工具。

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