陈则
从事流感病毒以及SARS病毒疫苗研究以及人类巨细胞病毒复制机理的解析。
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- 姓名:陈则
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学术头衔:
博士生导师
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学科领域:
微生物学
- 研究兴趣:从事流感病毒以及SARS病毒疫苗研究以及人类巨细胞病毒复制机理的解析。
陈则,男,1964年出生,博士,研究员。1988年获上海第二医科大学医学系医学学士学位,1997年3月获日本东京大学医学系医学博士学位,1997年3月至2000年3月在日本国立感染症研究所任协力研究员兼日本科学技术厅特别研究员。中科院武汉病毒研究所百人计划研究员、湖南师范大学特聘教授、中国微生物学会医学微生物与免疫学专业委员会副主任委员。从事流感病毒以及SARS病毒疫苗研究以及人类巨细胞病毒复制机理的解析。2001年在国际上首次报道了B型流感病毒核酸疫苗的研究。2003年首次报道了SARS病毒灭活疫苗的制备工艺, 2004年率先报道SARS病毒灭活疫苗在小鼠体内的免疫效果。近5年在SCI收录杂志上发表论文18篇。主持国家和省部级科技攻关项目20余项,在《Virology》、《Vaccine》等国际知名专业杂志上发表论文20余篇。
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陈则, Jianjun Chen a, , Fang Fang a, Xiangzhong Lia, Haiyan Changa, Ze Chen a, b, *
Vaccine 73(7005)4377-4328,-0001,():
-1年11月30日
The ability of a single dose of plasmid DNA encoding neuraminidase (NA) or hemagglutinin (HA) from influenza virus A/PR/8/34 (PR8)(H1N1) to protect against homologous virus infection was examined in BALB/c mice. In the present study, mice were immunized once with 30μg of NA or HA DNA by electroporation. Four weeks or 28 weeks after immunization, mice were challenged with a lethal dose of homologous virus and the ability of NA or HA DNA to protect the mice from influenza was evaluated. We found that a single inoculation of NA DNA could provide protection against influenza virus challenge as well as long-term protection against viral infection. Whereas, the mice immunized with a single dose of HA DNA could not be protected. In addition, neonatal mice immunized with a single dose of 30μg of NA DNA could be provided with significant protection against viral infection.
DNA vaccine, Influenza, Neuraminidase, Hemagglutinin
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陈则, Qiang Zhua, , Haiyan Changa, Yan Chena, Fang Fanga, Changyong Xuec, Fenghua Zhanga, Meizhen Qiva, Hanzhong Wangb, Bin Wangd, Ze Chena, b, *
Biochemical and Biophysical Research Communications 329(2005)87-94,-0001,():
-1年11月30日
Influenza virus infection frequently causes complications and some excess mortality in the patients with diabetes. Vaccination is an effective measure to prevent influenza virus infection. In this paper, antibody response and protection against influenza virus infection induced by vaccination were studied in mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized once or twice with inactivated influenza virus vaccine at various dosages. Four weeks after the first immunization or 1 week after the second immunization, the mice were challenged with influenza virus at a lethal dose. The result showed that the antibody responses in diabetic mice were inhibited. Immunization once with high dose or twice with low dose of vaccine provided full protection against lethal influenza virus challenge in diabetic mice, however, in healthy mice, immunization only once with low dose provided a full protection.
Diabetes mellitus, Influenza virus, Vaccine
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【期刊论文】Protection against influenza B virus infection by immunization with DNA vaccines
陈则, Ze Chena, b, Shin-etsu Kadowakia, Yukari Hagiwaraa, Tomoki Yoshikawaa, Tetsutaro Sataa, Takeshi Kurataa, Shin-ichi Tamuraa, *
Vaccine 19(2001)1446-1455,-0001,():
-1年11月30日
Protection against a lethal influenza B virus infection was examined in BALB/c mice immunized with plasmid DNAs encoding hemagglutinin (HA), neuraminidase (NA and NB) and nucleoprotein (NP) from the B/Ibaraki/2/85 virus. Each DNA vaccine was administered twice, 3 weeks apart, at a dose of 1 lag per mouse by particle-mediated DNA transfer to the epidermis (gene gun) or at a dose of 30 lag per mouse by electroporation into the muscle. Three weeks after the second vaccination, the mice were challenged with a lethal dose of homologous virus. HA and NA DNAs conferred complete protection against the lethal viral challenge, whereas NB and NP DNAs failed to provide protection against infection. Furthermore, protection in different strains of mice, BALB/c, B10 and C3H, immunized with HA and NA DNAs was compared. Both HA and NA DNAs conferred complete protection against the lethal challenge in all the tested mouse strains. These results suggest that both the HA and NA molecules can be used as vaccine components to provide effective protection against influenza B virus infection.
DNA vaccine, Influenza, Hemagglutinin, Neuraminidase
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【期刊论文】Cross-protection against a lethal influenza virus infection by DNA vaccine to neuraminidase
陈则, Ze Chena, b, Shin-etsu Kadowakia, Yukari Hagiwaraa, Tomoki Yoshikawaa, Kazutoshi Matsuoa, Takeshi Kurataa, Shin-ichi Tamuraa, *
Vaccine 18(2000)3214-3222,-0001,():
-1年11月30日
Cross-protection against a lethal influenza virus infection was examined in BALB/c mice immunized with plasmid DNAs encoding the neuraminidase (NA) from different subtype A viruses. Each NA-DNA was administered twice, 3 weeks apart, at the dose of 1μg per mouse by particle-mediated DNA transfer to the epidermis (gene gun) or at a dose of 30μg per mouse by electroporation into the muscle. Three weeks after the second vaccination, the mice were challenged with lethal doses of homologous or heterologous viruses and the ability of each NA-DNA to protect the mice from influenza was evaluated by determining the lung virus titers, body weight and survival rates. The H3N2 virus NA-DNA conferred cross-protection against lethal challenge with antigenic variants within the same subtype, but failed to provide protection against infection by a different subtype virus (H1N1). The degree of cross-protection against infection was related to titers of the cross-reacting antibodies. These results suggest that NA-DNA can be used as a vaccine component to provide effective protection against infection not only with homologous virus but also with drift viruses.
DNA vaccine, Influenza, Neuraminidase
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陈则, Ze Chen, Tomoki Yoshikawa, Shin-etsu Kadowaki, Yukari Hagiwara, Kazutoshi Matsuo, Hideki Asanuma, Chikara Aizawa, Takeshi Kurata and Shin-ichi Tamura
Journal of General Virology (1999), 80, 2559-2564.,-0001,():
-1年11月30日
Protection against influenza virus infection and antibody responses in mice vaccinated with plasmid DNAs encoding haemagglutinin (HA), neuraminidase (NA) and nucleoprotein (NP) were compared among BALB/c (H-2d), B10 (H-2b) and C3H (H-2k) mice. Mice were inoculated with each DNA construct twice, 3 weeks apart, at a dose of 1μg per mouse by particle-mediated DNA transfer (gene gun) to the epidermis. They were challenged with a lethal dose of the homologous virus 7 days after the second vaccination. NA-DNA provided significant protection in all strains of mouse, whereas HA-DNA afforded significant protection only in BALB/c mice. The serum antibody titres against NA or HA molecules in BALB/c, C3H and B10 mice were high, intermediate and low, respectively. NP-DNA failed to provide protection in any strain of mouse, and elicited low titres of anti-NP antibodies. These results suggest that NA-DNA can be used as a vaccine component to provide effective protection against influenza virus infection in various strains of mouse.
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陈则, Ze Chena, Kazutoshi Matsuoa, Hideki Asanumaa, Hidehiro Takahashia, Takuya Iwasakia, Yujiro Suzukib, Chikara Aizawab, Takeshi Kurataa, Shin-ichi Tamuraa, *
Vaccine 17(1999)653-659,-0001,():
-1年11月30日
The ability of plasmid DNA encoding hemagglutinin (HA), neuraminidase (NA) or matrix protein (M1) from in¯uenza virus A/PR/8/34 (PR8)(H1N1), and mixtures of these plasmid DNAs (HA+NA and HA+NA+M1) to protect against homologous or heterologous virus infection was examined in BALB/c mice. Each DNA was inoculated twice, 3 weeks apart, or four times, 2 weeks apart, at a dose of 1μg of each component per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after the last immunization, mice were challenged with a lethal homologous or heterologous virus and the ability of each DNA to protect the mice from in¯uenza was evaluated by observing lung virus titers and survival rates. The administration of a plasmid DNA mixture of either (HA+NA) or (HA+NA+M1) provided almost complete protection against the PR8 virus challenge, and this protection was accompanied by high levels of specific antibody responses to the respective components. The degree of protection afforded in these groups is significantly higher than that in mice given either HA- or NA-expressing DNA alone, which provided only a partial protection against PR8 challenge or that in mice given M1- expressing DNA, which failed to provide any protection. In addition, both of the plasmid DNA mixtures (HA+NA) and (HA+NA+M1) showed a slight tendency to provide cross-protection against an A/Yamagata/120/86 (H1N1) virus challenge, and this was accompanied by a relatively high level of cross-reacting antibodies. Thus, there was no clear difference between the ability of the HA+NA and HA+NA+M1 plasmid DNA mixtures in providing protection against either a PR8 or heterologous virus challenge. These results suggest that in mice immunized by gene gun, a mixture of plasmid DNAs encoding HA and NA can provide the most effective protection against the virus challenge. The addition of the M1-expressing plasmid DNA to this mixture does not enhance the degree of protection afforded.
DNA vaccine, Influenza, Hemagglutinin, Neuraminidase
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陈则, Z. Chen, * S. Sugano, * and S. Watanabe*, †,
Virology 258, 240-248 (1999),-0001,():
-1年11月30日
The human cytomegalovirus (HCMV) replication origin exhibits a strain-dependent difference in the number of copies of a 189-bp region: the AD169 and Towne strains contain one and three copies of the region, respectively. A nearly complete deletion of the 189-bp repeat region of the Towne strain does not eliminate the origin,s ability to initiate DNA synthesis. Here we report that the replication ability of the HCMV replication origin in infected cells disappeared after repiacements of an internal sequence (152 bp) of the 189-bp repeat region with λ DNA of identical and different lengths as well as after introduction of multiple nucleotide substitutions within the 152-bp internal sequence of the 189-bp repeat. ln contrast, a variation in the copy number of 189-bp region (either one or two copies) or an inversion of the 152-bp internal sequence of the 189-bp repeat maintained replication abilities similar to those of the wild-type origin of the Towne strain. These results indicate that the 189-bp repeat region within the HCMV replication origin is not just a dispensable spacer sequence but instead contains an irreplaceable sequence that may play a supporting role in HCMV DNA replication.
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陈则, Ze Chen*, Yasuhiro Sahashi*, Kazutoshi Matsuo*, Hideki Asanuma*, Hidehiro Takahashi*, Takuya Iwasaki*, Yujiro Suzuki†, Chikara Aizawa†, Takeshi Kurata* and Shin-ichi Tamura*‡
Vaccine 1998 Volume 16 Numeber 16,-0001,():
-1年11月30日
The ability of plasmid DNA encoding various influenza viral proteins from the A/PR/8/34 (H1N1) virus to protect against influenza was compared in BALB/c mice. The plasmid DNA encoded hemagglutinin (HA), neuraminidase (NA), matrix protein (M1), nucleoprotein (NP) or nonstructural protein (NS1) in a chicken β-actin-based expression vector (pCAGGS). Each DNA was inoculated twice 3 weeks apart at a dose of 1μg per mouse by particle-mediated DNA transfer to the epidermis (gene gun). Seven days after a second immunization, mice were challenged with the homologous virus and the ability of each DNA to protect mice from influenza was evaluated by decreased lung virus titers and increased srvival. Mice, given HA- or NA-expressing DNA, induced a high level of specific antibody response and protected well against the challenge virus. On the other hand, mice given M1-, NP-, or NS1-DNA fuiled to provide protection, although M1- and NP-DNAs did induce detectable antibody responses. These results indicate that both IIA- and NA-expressing DNAs for the surface glycoproteins are most protective against influenza from among the various viral protein-expressing DNAs used here.
DNA vaccine, influenza, hemagglutinin, neuraminidase
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