陈应华
个性化签名
- 姓名:陈应华
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
博士生导师
- 职称:-
-
学科领域:
药物化学
- 研究兴趣:
陈应华,男,1955年出生。1982年初毕业于武汉大学病毒学系,后留校工作。1983-1991年留学德国慕尼黑大学医学院免疫学研究所,获得慕尼黑大学理学博士学位和一年博士后训练。1991-1996年受聘到奥地利科学院艾滋病研究所和因斯布鲁克大学卫生研究所工作,为课题组组长。
1996年4月回国到清华大学生物系工作,同年7月被聘任为教授,1999年成为博士生导师。2000年被聘为教育部长江计划特聘教授。
1999-2002年任清华大学生物系副主任,并兼任清华大学医学科学研究中心副主任,药物研究所所长。
2002年?D至今 任清华大学生物系主任,兼任教育部蛋白质科学重点实验室副主任。
3次被评为清华大学先进工作者(1998,2000,2001年度)。2001年被评为清华大学优秀共产党员,2003年获教书育人奖。4次获得清华大学纪念梅贻琦学术论文二等奖 (1999-2002)
两度被国际著名学术杂志AIDS特邀进入审稿人数据库(1998,2000)
中国免疫学会终身会员,中国生化学会终身会员。1999-2002任中国免疫学会理事。
国家新药评审中心专家(2000-至今)
教育部提名国家科学技术奖(自然科学奖), 一等奖(2002年)
获1999年香港求是科技基金会杰出青年学者奖(生物/医学类);2000年国家杰出青年基金。
发表SCI论文75篇,其中责任作者/第一作者论文71篇。论文中有68篇为国际期刊论文,其中5 篇为国际期刊综述。有2 篇论文IF>12,7篇IF >5。
-
主页访问
2575
-
关注数
0
-
成果阅读
286
-
成果数
8
陈应华, Hengwen Yang, Canhui Lan, Yi Xiao, Ying-Hua Chen *
Immunology Letters 88 (2003) 27-30,-0001,():
-1年11月30日
The expression of HIV-1 coreceptors (CXCR4 and CCR5) on monocyte surface can be regulated by the ligand of CD14 (LPS), which stimulate the susceptibility of the cells to HIV-1. To investigate whether it exists potential association between CD14 and HIV-1 coreceptor CXCR4, we tested the impact of CD14-specific monoclonal antibodies (mAbs) upon CXCR4-dependent responses, such as SDF-induced chemotaxis and HIV Env-mediated membrane fusion. The anti-CD14 mAb TUK4 like CXCR4-specific mAb 12G5 could block SDF-induced chemotaxis of U937 cells in a dose-dependent manner, while another CD14-specific mAb UCHM-1 did not show any activity. More interestingly, syncytium assay indicated that only the CD14-specific mAb TUK4 inhibited HIV Env-mediated CXCR4-dependent cell fusion between U937 cells and HIV-1HXB2 Env transfected CHO cells distinctly, consistent with its activity against CXCR4-dependent chemotaxis. These results provided experimental evidence for existence of close association between CD14 and HIV coreceptor CXCR4 on human monocytic cells.
CD14, HIV coreceptor, CXCR4, Chemotaxis, Cell fusion
-
43浏览
-
0点赞
-
0收藏
-
0分享
-
176下载
-
0评论
-
引用
【期刊论文】HIV epitope-peptides in aluminum adjuvant induced high levels of epitope-specific antibodies
陈应华, Haijun Tian, Yi Xiao, Mei Zhu, Ying-Hua Chen*
International Immunopharmacology 1(2001)763-768,-0001,():
-1年11月30日
Some neutralizing epitopes on HIV-1 envelope proteins were shown to induce antibodies that could effectively inhibit the infection of different HIV-1 strains in vitro) But only very low levels of antibodies to these epitopes were determined in the HIV-1 infected individuals) In this study, the aluminum(alum)adjuvant to increase the immunogenicity of the neutralizing epitopes was used) Three epitope-peptides wC-(ELDKWAG)4, C-(RILAVERYLKD-G)2and C-(GPGRAFY)2 x, which contain three epitopes(ELDKWA, RILAVERYLKD, GPGRAFY)from the HIV-1 Env proteins, were synthesized and conjugated to carrier protein keyhole limpet hemocyanin(KLH)) The epitope-vaccines C-(ELDKWAG)4-KLH and C(RILAVERYLKD-G)2-KLH in alum induced high levels of epitope-specific antibodies recognizing the epitopes from epitope-peptides C-(ELDKWAG)4and C-(RILAVERYLKD-G)2, as well as the gp41 C-domain peptides P2 wCTSLIHSLIEESQNQQEKNEQELLELDKWA(aa 646-674)xand P1wLQARILAVERYLKDQQL(aa 583-599)x and the recombinant soluble gp41(rsgp41)bearing both epitopes(antibody titer in rabbit sera was 1:12800-25,600 dilution)) Immunoblotting analysis demonstrated that the antibodies in both antisera bound to rsgp41, indicating that both antibodies recognized the natural epitopes on rsgp41 protein) The epitope-vaccines C-(GPGRAFY)2-KLH induced moderate GPGRAFY epitope-specific antibody response with a titer of 1:6400) In contrast, as it was demonstrated in previous studies, the immunization with rgp160 induced weak antibody response to these three epitopes(titer of 1:400-1600)) This suggests that E pitope-peptides conjugated to KLH when infected with alum significantly increases immunogenicity of gp41 neutralizing epitopes providing a hope for the development of an HIV-1 vaccine)
Neutralizing epitope, Immunogenicity, Epitope-vaccine, HIV-1
-
42浏览
-
0点赞
-
0收藏
-
0分享
-
137下载
-
0评论
-
引用
【期刊论文】Mini Review Epitope-vaccine as a new strategy against HIV-1 mutation
陈应华, Yi Xiao a, b, Yun Lu a, Ying-Hua Chen a, *
Immunology Letters 77 (2001) 3-6,-0001,():
-1年11月30日
An effective vaccine is urgently needed to stop AIDS-epidemic. Up to now none of the candidate HIV-vaccines has been developed to prevent HIV-1 infection. A few neutralizing antibodies against HIV-1 enveloping proteins proved to be highly effective to neutralize different strains in vitro. Unfortunately, these antibodies are rare in infected humans, and have never yet been raised by a vaccine. The multiple sequential and antigenic variability of HIV-1 led to unprecedented difficulties in development of effective vaccines and anti-viral drugs. More and more experimental evidences indicated that HIV-1 mutants resulted in immune evasion may be a grave challenge for conventional strategy to prepare effective vaccines. We suggested that epitope-vaccine could be a new strategy to induce high levels of neutralizing antibodies with predefined epitope-specificity against HIV-1. Several candidate epitope-vaccines including mono-epitope-vaccine, multi-epitope-vaccine, epitope-vaccines in combination, were prepared and systematically studied in animal experiments. These studies provided experimental evidences that epitope-vaccine could be a new strategy to develop effective vaccines for prevention and immunotherapy against viral infection of HIV-l or other viruses.
Epitope-vaccine, Neutralizing epitope, CTL-epitope, HIV-1
-
25浏览
-
0点赞
-
0收藏
-
0分享
-
146下载
-
0评论
-
引用
【期刊论文】A common epitope on gp41, IFN-αand IFN-βinduces protective activity
陈应华, Ying-Hua Chen, Manfred P. Dierich
,-0001,():
-1年11月30日
nd human Iymphocytes, a highly conserved region (aa583-599; LQARILAV-ERYLKDQQL) was identified in gp41 as a binding site for human T cells and monocytes1-3, Gp41 could thus inhibit lym-phocyte proliferation4 and upregulate major histocompatibility complex (MHC) class I, class II and intercellular adhesion molecule 1 (ICAM-1) expression5-effects similar to those of human type I interferons. When we compared the sequences of gp41 and type I interferons, a similar epi-tope RILAV--YLKD was found in the im-munosuppressive domain (ISD) of gp41 and two regions in interferon α(IFN-α) (aa29-35 and 113-129), IFN-β(aa31-27 and 125-138) and IFN-ω(aa29-35 and 123-136) (Fig.1). Surprisingly, the common epitope exists within the receptor binding sites of gp41, IFN-α and IFN-β(Ref.6.) We characterized the common epitope and found increased levels of antibodies to IFN-αand IFN-βin20 HIV-infectedindividuals, compared with levels in normal healthy controls; these lev-els subsequently decreased with disease progression. Affinity-purified anti--gp41 an-tibody from HIV-infected individduals was shown to recognize human IFN-αand IFN-β. In addition, anti-IFN-αand IFN-β antibodies interacted with gp41 and its peptide(aa583-599), and inhibited gp41 binding to human lymphocytes. These results suggest that the common immunological epitope within gp41 induces incrased levels of an-tibodies that can interact with IFN-αand IFN-β. Gringeri et al. demonstrated that HIV-infected patients treated with an IFN-α vac-cine showed a significant reduction in the rate of disease progression, which was asso-ciated with an increase in IFN-αantibody titer and an increase in IFN-α-neutralizing capacity. The anti-IFN-α antibody was shown to recognize aa560-599 of HIV-1 gp41 (Ref. 7). These data suggest that the common immunological epitope within re-ceptor binding sites may be associated with protetive activity. Interestingly, a similar epitope in SIV gp32 could protect macaques from SIV infection89, indication that the common immunological epitope on gp41, IFN-αand IFN-β could be useful in the de-velopment of a vaccine strategy against HIV-infection.
-
33浏览
-
0点赞
-
0收藏
-
0分享
-
79下载
-
0评论
-
引用
【期刊论文】Epitope vaccine: a new strategy against HIV-1
陈应华, Ying-Hua Chen, Yi Xiao, Tianwei Yu
,-0001,():
-1年11月30日
It is generally agreed that the recombinant gp120 (rgp120) of HIV-1 could be developed as an antibody-mediated subunit vaccine against HIV-1. Unfortunately, Connor and co-workers have provided direct experimental evidence that rgp120 (monomer) does not protect individuals from HIV-1 infection1. In addition, Moore has reviewed studies of rgp120 subunit vaccines and proposed that a new strategy is needed to develop an effective vaccine against HIV-1 (Ref. 2). An epitope vaccine might be such a strategy. The epitope vaccine against HIV-1 uses much of the principal neutralizing determinant (PND) of the envelope (Env) protein (gp160) and belongs to a special type of synthetic peptide vaccine. Several epitopes on gp160 have been characterized as PNDs, for example, GPGRAF (Env aa316-321) on the V3 loop of gp120, ELDKWA (aa669-674) on the C-domain of gp41 and RILAVERYLKD (Env aa586-596) on the N-domain of gp41. It has been demonstrated that crossneutralizing antibodies elicited by peptides of the V3 loop bind to epitope GPGRAF, which undergoes restricted mutation from GPGRAF to GPG(R/K/Q)AF (Ref. 3). ELDKWA is a relatively conserved epitope. Recent sequence analysis of primary isolates from different HIV-1 subtypes suggests that the major determinant of monoclonal antibody (mAb) 2F5 corresponds to the amino acid sequence LDKW. Naturally occurring and in vitro-selected neutralization-resistant viruses contained D to N, D to E and K to N changes in the ELDKWA motif. These amino acid changes caused abrogation of 2F5-binding to ELDKWA (Ref. 4). Recent studies have attested the breadth of reactivity of 2F5 by the antibody's significant neutralization potency against African, Asian, American and European strains from clades A, B and E. Most of the viruses investigated were neutralized by 90% (Ref. 4). The epitope RILAVERYLKD has been shown to induce protective activity5. We have designed candidate synthetic peptide vaccines and compared immunogenicity of: (1) the recombinant gp160 and gp41 subunit vaccines; (2) peptide vaccines of the C-domain on gp41 (EnvIIIB aa646-674: C-TSLIHSLIEESQNQQEKNEQELLELDKWA) and the gp120 V3 loop (EnvIIIB aa301-328: C-TRPNNNTRKSIRIQRGPGRAFYTIGKI); and (3) epitope vaccines of ELDKWA on the C-domain of gp41 [C-(ELDKWAG)4-BSA] and GPGRAFY on gp120 [C-(GPGRAFY)4-P24EC]. In mice, the rgp160 subunit vaccine induced a very weak antibody response to both epitopes (ELDKWA and GPGRAFY), whereas both synthetic peptides conjugated with carrier protein BSA or carrier peptide P24EC (GPKEPFRDYVDRFYK-C) increased the epitope-specific antibody responses (increased antibody titre by two- to fourfold) to ELDKWA and GPGRAFY. Interestingly, both the ELDKWA and the GPGRAFY tetramer epitope vaccines induced a strong epitope-specific antibody response against ELDKWA and GPGRAFY, respectively, and the levels of ELDKWA- and GPGRAFY-specific antibodies increased two- to fourfold, compared with levels induced with the synthetic peptide vaccines (Table 1). These results indicate that the epitope vaccine could provide a new strategy to develop an effective vaccine against HIV-1 infection. Crystallographic analysis indicates that the binding of gp120 to both CD4 and a chemokine receptor induces conformational changes in gp41 from the native structure to the fusion-active structure. The exposed coiled coils create a fusion intermediate, in which the C-domain and N-domain are exposed6. Recent studies have demonstrated that a fusion-competent vaccine with broad neutralization of HIV primary isolates is associated with these fusion intermediates7,8, suggesting that
-
43浏览
-
0点赞
-
0收藏
-
0分享
-
107下载
-
0评论
-
引用
【期刊论文】Sequence variation and consensus sequence of V3 loop on HIV-1 gp120
陈应华, Haijun Tian, Canhui Lan, Ying-Hua Chen *
Immunology Letters 83 (2002) 231-233,-0001,():
-1年11月30日
Mutation in the V3 loop of HIV-1 gp120 could affect syncytium formation, virus infectivity and neutralization. To acquire more information of the V3 loop mutation, we analyzed amino acid sequences of the V3 loop of 24 504 isolates from most HIV-1 clades (including A, B, C, D, E, F, G and H clades). The consensus sequence of the V3 loop of each subtype with the highest frequency emerging on each position is constituted and the conservation of each amino acid in this region is also calculated. Exploring the restricted mutation of the V3 region could help to understand mechanism of HIV entry and to develop new strategy against HIV-1.
HIV-1, V3 loop, Sequence variation, Consensus sequence
-
28浏览
-
0点赞
-
0收藏
-
0分享
-
122下载
-
0评论
-
引用
【期刊论文】Candidate peptide vaccine induced protection against classical swine fever virus
陈应华, Xiao-Nan Dong a, b, Ke Wei a, Zu-Qiang Liu a, Ying-Hua Chen a, ∗
Vaccine 21 (2002) 167-173,-0001,():
-1年11月30日
Former investigations demonstrated that the envelope glycoprotein E2 could protect pigs from classical swine fever virus (CSFV). Based on these findings, we prepared synthetic peptide vaccine using E2 N-terminal antigenic units B/C and hoped to induce protective activity against lethal challenge of virulent CSFV strain Shimen. Five overlapped peptides sequence-covering amino acids 693-777 on E2 of Shimen were synthesized and then conjugated with bovine serum albumin (BSA), respectively. In the vaccination course, the candidate peptide vaccines in combination (multi-peptide vaccine (MPV)) were applied for immunization of pigs (n = 10) and induced strong antibody response against CSFV. It is subsequently demonstrated that this peptide vaccine could provide immunized pigs complete protection against lethal CSFV challenge as C-strain does, while all non-immunized pigs in negative control group manifested obvious typical symptoms and died during the second and third weeks after viral challenge. In order to confirm the neutralizing activity of the polyclonal antibodies induced by MPV, neutralization assay were carried out on rabbits. The live C-strain alone could ordinarily induce typical fever on rabbits. The typical fever of rabbits induced by the live C-strain could be inhibited by pre-incubation with the anti-sera (dilution 1:4 and 1:16) induced by MPV, but not inhibited by pre-incubation with the same anti-sera from which the antibodies against five peptides were removed by peptide-specific affinity chromatography, which indicates that these peptide-specific antibodies in the anti-sera induced by MPV provided protective activity against CSFV. Our finding provides a new way to develop marker vaccine against CSFV.
Classical swine fever virus, Synthetic peptide vaccine, Marker vaccine
-
48浏览
-
0点赞
-
0收藏
-
0分享
-
124下载
-
0评论
-
引用
【期刊论文】N-and C-domains of HIV-1 gp41: mutation, structure and functions
陈应华, Xiao-Nan Dong a, Yi Xiao a, Manfred P. Dierich b, Ying-Hua Chen a, *
Immunology Letters 75 (2001) 215-220,-0001,():
-1年11月30日
Recent studies demonstrated that the N- and C-domains of HIV-1 gp41 is involved in virus-mediated membrane fusion resulting in HIV-entry into the target cells. Up to now, viral mutation baffled many scientists to develop effective vaccines and drugs against HIV-1. To acquire more information of mutation of gp41 and to reveal the relationship of structure and function of the N- and C-domains, we compared and analyzed amino acid sequences of the gp41 ectodomain (aa 512-681) of 862 isolates from most HIV-1 clades (including A, B, C, D, E, F, G, H, I, J and O clades). A consensus sequence of the ectodomain with the highest frequency emerging on each position is constituted. The fusion domain and the N-domain belong to the most conserved regions in gp41, and most variable residues assemble partial to the C terminal of gp41. The hydrophobicity of each position is also calculated. The a and d positions in the N-domain for maintaining stabilization of the trimeric coiled coil interactions are highly conservative, and the e and g positions in the C-domain to retain the interaction show also highly conservative. The strange high conservation of the c residues may have an implication in the coiled coil structure. The highly conserved residues form the lining of the hydrophobic cavity and the deep cavity is an ideal target for small molecular inhibitors. On the C-terminal of the C-domain there is a highly conserved segment GIVQQQ. They are intimately involved in forming the three interfaces between neighboring helices. The function of the N- and C-domains, such as binding to the potential cellular receptor and inducing protective activities, are also discussed. These studies on the mutation, structure and functions of the N-and C-domains suggested that both domains become a new focus to develop effective vaccine and antiviral drugs in the new strategies.
HIV-1 gp41, N- and C-domains, Structure, Function
-
24浏览
-
0点赞
-
0收藏
-
0分享
-
125下载
-
0评论
-
引用