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Induction of adaptive immune responses against antigens incorporated within the capsid of simian virus 40.
Journal of General Virology ( IF 3.6 ) Pub Date : 2020-08-01 , DOI: 10.1099/jgv.0.001445
Kikue Saika 1 , Masahiko Kato 2 , Hideaki Sanada 2 , Sho Matsushita 1, 3 , Masanori Matsui 4 , Hiroshi Handa 5 , Masaaki Kawano 1
Affiliation  

Simian virus 40 (SV40) is a monkey polyomavirus. The capsid structure is icosahedral and comprises VP1 units that measure 45 nm in diameter. Five SV40 VP1 molecules form one pentamer subunit, and a single icosahedral subunit comprises 72 pentamers; a single SV40 VP1 capsid comprises 360 SV40 VP1 molecules. In a previous study, we showed that an influenza A virus matrix protein 1 (M1) CTL epitope inserted within SV40 virus-like particles (VLPs) induced cytotoxic T lymphocytes (CTLs) without the need for an adjuvant. Here, to address whether SV40 VLPs induce adaptive immune responses against VLP-incorporated antigens, we prepared SV40 VLPs containing M1 or chicken ovalbumin (OVA). This was done by fusing M1 or OVA with the carboxyl terminus of SV40 VP2 and co-expressing them with SV40 VP1 in insect cells using a baculovirus vector. Intraperitoneal (i.p.) or intranasal administration of SV40 VLPs incorporating M1 induced the production of CTLs specific for the M1 epitope without the requirement for adjuvant. The production of antibodies against SV40 VLPs was also induced by i.p. administration of SV40 VLPs in the absence of adjuvant. Finally, the administration of SV40 VLPs incorporating OVA induced anti-OVA antibodies in the absence of adjuvant; in addition, the level of antibody production was comparable with that after i.p. administration of OVA plus alum adjuvant. These results suggest that the SV40 capsid incorporating foreign antigens can be used as a vaccine platform to induce adaptive immune responses without the need for adjuvant.

中文翻译:

诱导针对猿猴病毒40衣壳中掺入的抗原的适应性免疫反应。

猿猴病毒40(SV40)是猴多瘤病毒。衣壳结构为二十面体,并包含直径为45 nm的VP1单元。五个SV40 VP1分子形成一个五聚体亚基,一个二十面体亚基包含72个五聚体;单个SV40 VP1衣壳包含360个SV40 VP1分子。在先前的研究中,我们显示了在SV40病毒样颗粒(VLP)中插入的甲型流感病毒基质蛋白1(M1)CTL表位可诱导细胞毒性T淋巴细胞(CTL),而无需佐剂。在这里,为了解决SV40 VLP是否诱导针对结合VLP的抗原的适应性免疫反应,我们制备了含有M1或鸡卵清蛋白(OVA)的SV40 VLP。通过将M1或OVA与SV40 VP2的羧基末端融合,并使用杆状病毒载体将它们与SV40 VP1在昆虫细胞中共表达来完成。掺入M1的SV40 VLP的腹膜内(ip)或鼻内给药可诱导产生对M1表位具有特异性的CTL,而无需佐剂。在不存在佐剂的情况下,通过ip给药SV40 VLP也诱导了针对SV40 VLP的抗体的产生。最后,在没有佐剂的情况下,施用掺入OVA诱导的抗OVA抗体的SV40 VLP。另外,抗体的产生水平与腹膜内注射OVA加明矾佐剂的水平相当。这些结果表明,掺入外源抗原的SV40衣壳可以用作疫苗平台来诱导适应性免疫反应,而无需佐剂。)或掺入M1的SV40 VLP鼻内给药可诱导产生对M1表位特异的CTL,而无需佐剂。在不存在佐剂的情况下,通过ip给药SV40 VLP也诱导了针对SV40 VLP的抗体的产生。最后,在没有佐剂的情况下,施用掺入OVA诱导的抗OVA抗体的SV40 VLP。另外,抗体的产生水平与腹腔注射OVA加明矾佐剂的腹腔注射水平相当。这些结果表明,掺入外源抗原的SV40衣壳可以用作疫苗平台来诱导适应性免疫反应,而无需佐剂。)或掺入M1的SV40 VLP鼻内给药可诱导产生对M1表位特异的CTL,而无需佐剂。在不存在佐剂的情况下,通过ip给药SV40 VLP也诱导了针对SV40 VLP的抗体的产生。最后,在没有佐剂的情况下,施用掺入OVA诱导的抗OVA抗体的SV40 VLP。另外,抗体的产生水平与腹膜内注射OVA加明矾佐剂的水平相当。这些结果表明,掺入外源抗原的SV40衣壳可以用作疫苗平台来诱导适应性免疫反应,而无需佐剂。在没有佐剂的情况下施用掺入OVA诱导的抗OVA抗体的SV40 VLP;另外,抗体的产生水平与腹腔注射OVA加明矾佐剂的腹腔注射水平相当。这些结果表明,掺入外源抗原的SV40衣壳可以用作疫苗平台来诱导适应性免疫反应,而无需佐剂。在没有佐剂的情况下施用掺入OVA诱导的抗OVA抗体的SV40 VLP;另外,抗体的产生水平与腹腔注射OVA加明矾佐剂的腹腔注射水平相当。这些结果表明,掺入外源抗原的SV40衣壳可以用作疫苗平台来诱导适应性免疫反应,而无需佐剂。
更新日期:2020-08-27
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