A CTL-based liposomal vaccine capable of inducing protection against heterosubtypic influenza viruses in HLA-A*0201 transgenic mice
A CTL-based liposomal vaccine capable of inducing protection against heterosubtypic influenza viruses in HLA-A*0201 transgenic mice
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DOI：
10.1016/j.bbrc.2009.12.100
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发表时间：
2010-01-15
影响因子：
3.1
通讯作者：
Uchida, Tetsuya
中科院分区：
文献类型：
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作者：
Matsui, Masanori;Kohyama, Shunsuke;Uchida, Tetsuya
目前针对流感的疫苗接种策略是诱导产生针对病毒表面抗原的抗体。然而，流感病毒表面抗原的频繁变化使病毒能够避免抗体介导的免疫。另一方面，已知针对甲型流感病毒的内部抗原的细胞毒性T淋巴细胞（CTL）群体与流感病毒亚型广泛交叉反应。在本研究中，评价了具有源自流感病毒的高度保守的内部抗原的CTL表位肽的脂质体缀合物保护免受流感病毒感染的能力。与肽M1 58-66（存在于M1编码区的氨基酸序列内的HLA-A（*）0201结合CTL表位）的脂质体缀合物成功地在HLA-A（*）0201转基因小鼠中诱导抗原特异性CD 8（+）T细胞和CTL。此外，经鼻感染H1N1或H3 N2病毒后，免疫小鼠肺中的病毒复制被显著抑制。这些保护性活动在免疫后至少持续6个月。因此，这些结果表明，脂质体偶联的CTL表位肽来源于高度保守的内部抗原的流感病毒可能适用于开发疫苗，诱导保护免受感染与异亚型流感病毒。(c)2009 Elsevier Inc. All rights reserved.
The current vaccination strategy against influenza is to induce the production of antibodies directed against surface antigens of viruses. However, the frequent changes in the surface antigens of influenza viruses allow the viruses to avoid antibody-mediated immunity. On the other hand, it is known that cytotoxic T-lymphocyte (CTL) populations directed against internal antigens of influenza A virus are broadly cross-reactive to influenza virus subtypes. In the present study, liposomal conjugates with CTL epitope peptides derived from highly conserved internal antigens of influenza viruses were evaluated for their ability to protect against infection with influenza viruses. Liposomal conjugates with peptide M1 58-66, an HLA-A(*)0201-binding CTL epitope present within the amino-acid sequence of the M1 coding region, successfully induced antigen-specific CD8(+) T-cells and CTLs in HLA-A(*)0201-transgenic mice. Moreover, after nasal infection with either the H1N1 or H3N2 virus, viral replication in the lung was significantly inhibited in the immunized mice. These protective activities lasted at least 6 months after the immunization. Thus, these results suggest that liposome-coupled CTL epitope peptides derived from highly conserved internal antigens of influenza viruses might be applicable to the development of vaccines that induce protection against infection with heterosubtypic influenza viruses. (c) 2009 Elsevier Inc. All rights reserved.