1.The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects.
Huan LIU ; Xiaojie SU ; Lulu SI ; Lu LU ; Shibo JIANG
Protein & Cell 2018;9(7):596-615
A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives: (1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.
AIDS Vaccines
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chemistry
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immunology
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Antibodies, Neutralizing
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immunology
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HIV Antibodies
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immunology
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HIV Envelope Protein gp41
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immunology
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HIV-1
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chemistry
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immunology
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Humans
2.Establishment of a double-antigen sandwich ELISA for detecting total antibodies to human immunodeficiency virus type 1/2.
Hongxia HE ; Panyong MAO ; Jun HOU ; Shiwen HONG ; Lei ZHU ; Yan HU ; Yanping BAI
Chinese Journal of Experimental and Clinical Virology 2002;16(3):288-291
OBJECTIVETo describe and evaluate a double-antigen sandwich ELISA for detecting human immunodeficiency virus type 1/2 (HIV-1/2) specific antibodies.
METHODSThe peptides gp41.1(sp1), gp41.2(sp2), gp120(sp3) and p24(sp4) of HIV-1 and gp36(sp5) of HIV-2 were artificially synthesized. Then sp1, sp3, sp4 and sp5 were used as coating antigens; sp1, sp2, sp4 and sp5 labeled with HRP were used as conjugates in this sandwich ELISA.
RESULTSThe specificity and sensitivity of the assay were both 100% in detecting anti-HIV of 40 control sera of the second generation panel, higher than indirect ELISA (specificity 90% and sensitivity, 65%, respectively). All of 210 sera from individuals with other diseases were negative for anti-HIV. The consistency rate was 100% when our sandwich ELISA and Abbott HIVAB were used to detect anti-HIV in 90 healthy blood donors and 88 HIV infected individuals.
CONCLUSIONSThe results showed that this sandwich ELISA for detection of anti-HIV is specific, sensitive and convenient, and it is suitable for screening blood donors and detecting HIV infection.
Enzyme-Linked Immunosorbent Assay ; methods ; HIV Antibodies ; blood ; HIV Infections ; blood ; virology ; HIV-1 ; immunology ; HIV-2 ; immunology ; Humans
3.T cell immune response during HIV infection and immune escape.
Yan-min WAN ; Chao CHOU ; Xiao-yan ZHANG ; Jian-qin XU
Chinese Journal of Virology 2008;24(4):326-333
HIV Infections
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immunology
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HIV-1
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genetics
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immunology
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Humans
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Mutation
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T-Lymphocytes
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immunology
4.Knowledge and attitude on HIV/AIDS prevention of injection drug addicts in Dien Bien & Dong Thap provinces
Journal of Preventive Medicine 2007;17(2):55-58
Background: Today, the incidence of HIV has a tendency to increase in high risk population and other populations in Vietnam. HIV epidemic in Vietnam is closely assocciated with the situation of injection drug addicts and female sex workers. Objective: To study knowledge and attitude on HIV/AIDS prevention of injection drug addicts in Dien Bien & Dong Thap provinces. Subjects and method: A cross-sectional, descriptive, investigation using the questionnaire of the Ministry of Health was conducted in 731 injection drug addicts in the 9 districts/towns in \u0110ien Bien province (Dien Bien Phu town, Dien Bien, Tuan Giao, Phong Tho and Muong Lay district) and Dong Thap province (Cao Lanh town, Sa Dec, Hong Ngu and Tam Nong district), from August/2004 to January/2005. Results and Conclusion: 71.5%-81.3% of injection drug addicts had correct knowledge about the ways of HIV/AIDS transmission. 65.2%-79.9% of injection drug addicts knew HIV/AIDS prevention methods. 98.5% of injection drug addicts said that thay had been ready to look after their relatives infected with HIV/AIDS. 71.4%-98.7% ofinjection drug addictshad the attitude of keeping normal relationship with HIV infected subjects. 76.7% of injection drug addicts agreed that teachers with HIV could continute to teach.
HIV/ immunology
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Health Knowledge
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Attitudes
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Practice
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5.Advances in the Immunogenic Design of HIV-1 Vaccine.
Xiaohong ZHANG ; Tao WANG ; Xiaofang YU
Chinese Journal of Virology 2016;32(1):88-92
A safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is expected to have a considerable impact on elimination of acquired immune deficiency syndrome. Despite decades of effort, an effective vaccine against HIV-1 remains elusive. In recent years, the Thai HIV Vaccine Efficacy Trial (known as RV144) showed a reduction in HIV-1 acquisition by 31%, but this agent could not delay disease progression in vaccinated individuals. Clinical analyses of experimental data and experiments in vitro have revealed two main types of immunogen design: induction of broad-spectrum neutralizing antibody (bNAb) and cytotoxic T lymphocyte (CTL) responses. bNAb can prevent or reduce acquisition of infection, and its main immunogens are virus-like particles, natural envelope trimers and stable bNAb epitopes. An effective CTL response can slow-down viral infection, and its main immunogens are "mosaic" vaccines, "conserved immunogens", and the "fitness landscape" of HIV-1 proteins. This review summarizes the strategies as well as progress in the design and testing of HIV-1 immunogens to elicit bNAb and CTL responses.
AIDS Vaccines
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genetics
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immunology
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Animals
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Drug Design
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HIV Antibodies
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immunology
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HIV Infections
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immunology
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prevention & control
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virology
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HIV-1
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genetics
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immunology
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Humans
6.Development of a rapid test kit for antibody to HIV by nano immunomagnetic lateral flow method.
Fa-qing YANG ; Tony LEE ; Chao-nan WANG ; Shu-ye SUN ; Shan-shan LI ; Hui TIAN
Chinese Journal of Experimental and Clinical Virology 2010;24(3):235-237
OBJECTIVETo develop a rapid test kit for antibody to HIV by nano immunomagnetic lateral flow method.
METHODSA rapid test kit was developed by conjugation of the HIV antigen gp41 and gp36 to 200nm super paramagnetic particles by carbodiimide (EDC) and coating of the HIV antigen gp41 and gp36 to nitrocellulose membrane. Then the kit was evaluated with serials of experiments.
RESULTSThe kit was qualified with examination of national reference panel of anti-HIV antibody for colloidal gold diagnostic kit. The sensitivity was 100% by tested with 20 HIV antibody positive sera, the specificity was 98.5% by tested with 600 HIV antibody negative sera, respectively. The stability of the kit was over 12 month by storage at room temperature.
CONCLUSIONA diagnostic kit for antibody to HIV was developed with the advantages of convenience, rapid test, good stability and point of care.
Antibodies, Anti-Idiotypic ; immunology ; Gold Colloid ; chemistry ; HIV ; immunology ; isolation & purification ; HIV Antibodies ; HIV Envelope Protein gp41 ; HIV Infections ; diagnosis ; HIV Seropositivity ; blood ; HIV-1 ; immunology ; isolation & purification ; Immunomagnetic Separation ; methods ; Molecular Biology ; methods ; Nanotechnology ; Reagent Kits, Diagnostic
7.Identification of HIV-1 specific T lymphocyte responses in highly exposed persistently seronegative Chinese.
Hong-wei LIU ; Kun-xue HONG ; Jun MA ; Lin YUAN ; Sha LIU ; Jian-ping CHEN ; Yuan-zhi ZHANG ; Yu-hua RUAN ; Jian-qing XU ; Yi-ming SHAO
Chinese Medical Journal 2006;119(19):1616-1621
BACKGROUNDStudies of highly exposed persistently seronegative (HEPS) individuals may provide valuable information on mechanisms of protection and on vaccine design. Cellular immune responses play a critical role in containing human immunodeficiency virus. However, the cellular immune responses in HEPS individuals have not been thoroughly assessed at the entire viral genome level.
METHODSTen HEPS Chinese with a history of frequent penetrative vaginal intercourse (mean frequency, at least once a week), with some unprotected sexual contact occurring in the weeks or days immediately before enrollment, 25 HIV-1 seropositive individuals, 10 HIV-1-seronegative healthy individuals with low-risk sexual behavior and no history suggestive of exposure to HIV-1 infection were enrolled. HIV-1-specific T cell responses were comprehensively analyzed by an interferon-gamma Elispot assay against 770 overlapping peptides spanning all HIV-1 proteins.
RESULTSHIV-1-specific T-cell responses of interferon-gamma secretion were identified in 3 (30%) out of 10 HEPS individuals; the specific cytotoxic T lymphocytes were targeted at Pol (2/10), Env (2/10), and Tat (1/10). HIV-1-specific T-cell responses of interferon-gamma secretion were identified in 20 (80%) out of 25 seropositive intravenous drug users (IDUs), revealing that all HIV-1 proteins and protein subunits could serve as targets for HIV-1-specific CD8(+) T cell responses with 85% recognizing Gag, 80% recognizing Nef, 75% recognizing Pol, 60% recognizing Env, 55% recognizing Vpu, 45% recognizing Vpr, 20% recognizing Vif, 20% recognizing Tat and 15% recognizing Rev in these seropositive individuals. None of the seronegative healthy individuals gave the positive T-cell responses.
CONCLUSIONSAbout 30% of HEPS Chinese mounted HIV-1 specific T cell immune responses. Cell-mediated immunity against HIV-1 may be developed through non-productive infections.
Adult ; Female ; HIV Seronegativity ; immunology ; HIV-1 ; immunology ; Humans ; Interferon-gamma ; biosynthesis ; Male ; Receptors, CCR5 ; genetics ; T-Lymphocytes, Cytotoxic ; immunology
9.Establishment and evaluation of the diagnostic kit for anti-HIV1/2 antibody and P24 antigen.
Yan HU ; Jun HOU ; Yan-qing FENG ; Chang-fang FENG ; Su-juan SHI ; Hong-hui H SHEN ; Zhi-jie WANG ; Bao-jun WANG ; Pan-yong MAO
Chinese Journal of Experimental and Clinical Virology 2007;21(4):391-393
OBJECTIVETo establish and evaluate an Enzyme Immunoassay diagnostic kit combined with anti-HIV1/2 antibody and P24 antigen for shortening the examination window period of HIV infection in HIV laboratory diagnosis.
METHODSThe enzyme-linked reaction plates was coated by anti-HIV P24 monoclonal antibody and HIV 1/2 antigen. Labeling HIV1/2 antigen and anti-HIV P24 polyclonal antibody with horseradish peroxidase, setup an integrated ELISA kit for detecting anti-HIV-1/2 antibody and HIV P24 antigen, and evaluate the specificity and sensitivity of this kit.
RESULTSThe sensitivity of testing P24 antigen was up to 0.2 ng/ml. 78 serum samples of patients with AIDS, 85 serum samples of healthy people were compared with Abbott EIA kit, the coincidence was 100%. 12 051 sera from normal persons and patients were examined, the sensitivity of 100 %and specificity of 99.62 %, respectively.
CONCLUSIONThe anti-HIV1/2 antibody and HIV P24 antigen can be measured at the same time using this EIA kit, while the examination window period of HIV infection is shortened. Thus, the method is suitable for laboratory diagnosis and epidemiological investigation.
Enzyme-Linked Immunosorbent Assay ; HIV Antibodies ; blood ; HIV Core Protein p24 ; blood ; HIV-1 ; immunology ; HIV-2 ; immunology ; Humans ; Reagent Kits, Diagnostic
10.Retrospective study on HIV infection among blood donors in Zhejiang Province over 11-year period (1993 - 2004).
Zhong-Hua MENG ; Jin YANG ; Hua-Ping ZHOU ; Li-Xing YAN
Journal of Experimental Hematology 2006;14(6):1231-1233
To determine HIV prevalence among blood donors in Zhejiang Province from 1993 to 2004 years, almost 6,600, 000 blood donors information were collected and analyzed. Every sample was screened for markers of HIV-1 and HIV-2 by using commercially available ELISA kits twice, and Western blot for confirmation if positive or suspicious result appeared. The results indicated that during the study period, prevalence rate of HIV infection was 0.85/1000 donors (0.085%), with the rising tendency from 1:600000 in 1995 to 1:37500 in 2004. The prevalence of HIV infection in Zhejiang donors was significantly lower than that in donors of other provinces, prevalence of HIV infection in male was higher than that in female. In recent years, the prevalence of HIV in blood donors was obviously increased, but the difference among various populations began to reduce. It is concluded that in a low HIV prevalence area like Zhejiang province where no obvious AIDS occurred, risk for the expansion of the HIV epidemic was on the increase. Screening procedure used in transfusion services nowaday is reliable, but a comprehensive approach is required to make the blood more safe.
Blood Donors
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China
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epidemiology
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Enzyme-Linked Immunosorbent Assay
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Female
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HIV Infections
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prevention & control
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HIV Seroprevalence
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trends
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HIV-1
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immunology
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HIV-2
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immunology
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Humans
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Male
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Retrospective Studies
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Transfusion Reaction