期刊
ANTIVIRAL RESEARCH
卷 81, 期 3, 页码 253-260出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2008.12.009
关键词
H5N1 influenza A virus; Hemagglutinin; CTL epitope; DNA vaccine
资金
- National High Technology Research and Development Program of China [2006AA02Z463]
- National Fund for Fostering Talents of Basic Sciences [J0630648]
DNA vaccination is an effective means of eliciting both humoral and cellular immune responses. The hemagglutinin (HA) surface protein of influenza A virus is a major target of protective antibody responses induced by virus infection or by vaccination and is widely considered to be the antigen of choice for an influenza vaccine. Cytotoxic T lymphocyte (CTL) responses directed against the conserved nucleoprotein (NP) are thought to play an important role in clearing virus and promoting survival and recovery from influenza. In this study, we developed a novel DNA vaccine approach using a chimeric plasmid consisting of the HA of H5N1 influenza virus in which an MHC class I-restricted NP-specific CTL epitope (NP147-155) was inserted. Immunogenicity and antiviral efficacy of this vaccine was assessed in mouse models. A similar level of HA expression was achieved in 293T cells transfected with pHA/NP147-155 compared to that with pHA. Besides eliciting the specific anti-HA antibody responses, vaccination using pHA/NP147-155 in mice induced NP epitope-specific CD8(+) T cell responses, which are generally not inducible by vaccination with pHA alone. After H5N1 influenza virus challenge, BALB/c mice vaccinated with pHA/NP147-155 exhibited reduced inflammation severity and lung viral titers compared to those vaccinated with pHA. Our work may contribute to improvement of HA-based influenza DNA vaccines. (c) 2008 Elsevier B.V. All rights reserved.
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