展示于T4噬菌体表面的经口服递送的口蹄疫病毒衣壳原聚体疫苗:对小鼠效力挑战的100%保护率

Orally delivered foot-and-mouth disease virus capsid protomer vaccine displayed on T4 bacteriophage surface: 100% protection from potency challenge in mice.

作者信息

Ren Z J, Tian C J, Zhu Q S, Zhao M Y, Xin A G, Nie W X, Ling S R, Zhu M W, Wu J Y, Lan H Y, Cao Y C, Bi Y Z

机构信息

Expression BioSciences Inc., Somerset, NJ 08873, USA.

出版信息

Vaccine. 2008 Mar 10;26(11):1471-81. doi: 10.1016/j.vaccine.2007.12.053. Epub 2008 Jan 24.

Abstract

An orally delivered foot-and-mouth disease (FMD) vaccine has not previously been reported. By using a T4 bacteriophage nanoparticle surface gene-protein display system (T4-S-GPDS), we created a foot-and-mouth disease virus (FMDV) entire capsid protein vaccine candidate. On the T4 phage surface SOC site, a full length FMDV capsid precursor polyprotein (P1, 755 aa) and proteinase 3C (213 aa) derived from an infected pig of serotype O strain GD-10 (1999), were separately displayed on different T4 phage particle surfaces through inserting their coding region DNAs into the T4 phage genome, yielding phage strains T4-P1 and T4-3C. We also constructed a series of FMDV sub-full length capsid structural protein (subunit) containing T4 phage recombinant vaccines. Both sucking and young BALB/c mice were used as two kinds of FMDV vaccine potency evaluation models. Many groups of both model mice were vaccinated orally or by subcutaneous injection with varying FMDV-T4 phage recombinant vaccines, with and without addition of adjuvant, then challenged with a lethal dose of cattle source virulent FMDV. In the case of immunization with a mixture of phage T4-P1 and phage T4-3C particles without any adjuvant added, all mice were 100% protected following either oral or injection immunization, whereas 100% of the control, non-immunized mice and mice immunized with only T4 phage vector Z1/Zh(-) or wild-type T4(+)D phage died; in contrast, with FMDV subunit vaccine, less than 75% protection followed the same potency challenge in both mice model groups. In addition, two pigs immunized with a phage T4-P1 and phage T4-3C mix were protected upon housing together with infected pigs. This study represents a clear example of how FMD and other pathogenic disease vaccines can be prepared by a simple and efficient bacteriophage route.

摘要

此前尚未有口服的口蹄疫(FMD)疫苗的相关报道。通过使用T4噬菌体纳米颗粒表面基因-蛋白质展示系统(T4-S-GPDS),我们构建了一种口蹄疫病毒(FMDV)全衣壳蛋白疫苗候选物。在T4噬菌体表面的SOC位点,将源自O型GD-10(1999年)血清型感染猪的全长FMDV衣壳前体多聚蛋白(P1,755个氨基酸)和蛋白酶3C(213个氨基酸),通过将它们的编码区DNA插入T4噬菌体基因组,分别展示在不同的T4噬菌体颗粒表面,得到噬菌体菌株T4-P1和T4-3C。我们还构建了一系列含有FMDV亚全长衣壳结构蛋白(亚基)的T4噬菌体重组疫苗。将吮乳期和幼年BALB/c小鼠用作两种FMDV疫苗效力评估模型。多组这两种模型小鼠通过口服或皮下注射不同的FMDV-T4噬菌体重组疫苗进行免疫,添加或不添加佐剂,然后用致死剂量的牛源强毒FMDV进行攻毒。在用未添加任何佐剂的噬菌体T4-P1和噬菌体T4-3C颗粒混合物进行免疫的情况下,所有小鼠经口服或注射免疫后均得到100%的保护,而100%的对照未免疫小鼠以及仅用T4噬菌体载体Z1/Zh(-)或野生型T4(+)D噬菌体免疫的小鼠死亡;相比之下,对于FMDV亚单位疫苗,在两种小鼠模型组中,相同效力攻毒后的保护率均低于75%。此外,用噬菌体T4-P1和噬菌体T4-3C混合物免疫的两只猪在与感染猪共同饲养时得到了保护。这项研究是通过简单有效的噬菌体途径制备FMD及其他致病性疾病疫苗的一个明显实例。

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