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反向胶束包封重组杆状病毒作为口服疫苗对 H5N1 感染的小鼠。

Reverse micelle-encapsulated recombinant baculovirus as an oral vaccine against H5N1 infection in mice.

机构信息

Animal Health Biotechnology, Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.

出版信息

Antiviral Res. 2010 May;86(2):180-7. doi: 10.1016/j.antiviral.2010.02.315. Epub 2010 Feb 12.

DOI:10.1016/j.antiviral.2010.02.315
PMID:20153776
Abstract

Induction of mucosal immunity through oral immunization is an effective way to control influenza infection. In this study, baculovirus displaying influenza hemagglutinin was encapsulated within a reverse micelle structure of phosphatidylcholine and delivered into the gastrointestinal tract of mice to study its efficacy as an oral vaccine against cross-clade H5N1 infection. Mice vaccinated with encapsulated baculovirus displaying HA (En-BacHA) showed significantly enhanced HA specific serum IgG and mucosal IgA antibodies, and higher hemagglutination inhibition (HI) titers, when compared to its non-encapsulated form (BacHA). Estimation of serum neutralizing antibodies also indicated that En-BacHA formulation was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1, clade 4.0 and clade 8.0). Further, mice vaccinated with En-BacHA alone were able to confer 100% protection against 5MLD50 of HPAI heterologous H5N1 strain (clade 1). Inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant in the vaccine formulation did not show any significant effect in both systemic and mucosal immune responses. Oral delivery of encapsulated recombinant H5 HA expressed on baculovirus surface is an effective way to prime the immune system against H5N1 infection in mice and will have no biosafety concerns associated with their production or administration.

摘要

通过口服免疫诱导黏膜免疫是控制流感感染的有效方法。在这项研究中,展示流感血凝素的杆状病毒被包裹在磷脂酰胆碱的反向胶束结构内,并递送到小鼠的胃肠道中,以研究其作为针对跨群 H5N1 感染的口服疫苗的功效。与未包裹的形式(BacHA)相比,用包裹的展示 HA 的杆状病毒(En-BacHA)免疫的小鼠显示出明显增强的 HA 特异性血清 IgG 和黏膜 IgA 抗体,以及更高的血凝抑制(HI)滴度。对血清中和抗体的估计也表明,En-BacHA 配方能够诱导针对异源 H5N1 株(群 1.0、群 2.1、群 4.0 和群 8.0)的强烈跨群中和作用。此外,单独用 En-BacHA 免疫的小鼠能够对 5MLD50 的高致病性禽流感异源 H5N1 株(群 1)提供 100%的保护。在疫苗配方中包含重组霍乱毒素 B 亚单位作为黏膜佐剂并没有在系统和黏膜免疫反应中显示出任何显著效果。在杆状病毒表面表达的包裹的重组 H5 HA 的口服递送是在小鼠中针对 H5N1 感染引发免疫系统的有效方法,并且不会产生与其生产或管理相关的任何生物安全问题。

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