Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design
Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design
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DOI：
10.1002/eji.200636959
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发表时间：
2008-01-01
影响因子：
5.4
通讯作者：
Bachmann, Martin F.
中科院分区：
文献类型：
--
作者：
Bessa, Juliana;Schmitz, Nicole;Bachmann, Martin F.
鼻内（i.n.）免疫的目的是诱导局部和全身免疫应答。在本研究中，我们评估了基于源自RNA噬菌体Q β的病毒样颗粒（VLP）的疫苗平台，用于i.n.次免疫我们发现，两个I.N.和皮下（s.c.）Q β-VLP的施用在血清和肺中引起强的和可比较的特异性IgG应答。令人惊讶的是，这两种途径也诱导血清中高水平的特异性伊加。相比之下，只有i.n. Q β-VLP的施用导致肺中局部伊加的产生。i.n.对B细胞应答的有效诱导VLP的给药还得到了大量生发中心（GC）以及脾中记忆B细胞和骨髓中浆细胞的存在的支持。对于VLP本身获得的结果可以扩展到共价连接到其上的抗原。用展示流感病毒衍生的M2蛋白胞外结构域的VLP免疫小鼠，导致强烈的M2特异性抗体应答以及抗病毒保护。相反，i.n.用展示p33肽（淋巴细胞性脉络丛脑膜炎病毒的主要CTL表位）的VLP免疫诱导相对低效的细胞毒性T细胞应答，导致低数量的特异性T细胞和差的效应细胞分化。总之，这些结果表明，有效的抗体为基础的疫苗是可以实现的，通过i. n。施用展示特异性抗原的QP-VLP。
Intranasal (i.n.) immunization aims to induce local as well as systemic immune responses. In the present study, we assessed a vaccine platform based on virus-like particles (VLP) derived from the RNA phage Q beta for i.n. immunization. We found that both i.n. and subcutaneous (s.c.) administration of Q beta-VLP elicited strong and comparable specific IgG responses in serum and lung. Surprisingly, both routes also induced high levels of specific IgA in serum. In contrast, only i.n. administration of Q beta-VLP resulted in local IgA production in the lung. Efficient induction of B cell responses by i.n. administration of VLP was further supported by the presence of large numbers of germinal centers (GC) as well as memory B cells in the spleen and plasma cells in the bone marrow. Results obtained for the VLP itself could be extended to an antigen covalently attached to it. Specifically, i.n. immunization of mice with VLP displaying the influenza virus derived ectodomain of the M2 protein resulted in strong M2-specific antibody responses as well as anti-viral protection. In contrast, i.n. immunization with VLP displaying p33 peptide, the major CTL epitope of lymphocytic choriomeningitis virus, induced relatively inefficient cytotoxic T cell responses, resulting in low numbers of specific T cells and poor effector cell differentiation. Taken together, these results suggest that effective antibody-based vaccines are achievable by i.n. administration of QP-VLP displaying specific antigens.