1.Prospectives of nucleic acid vaccine technology platform in preventive vaccine development
Xuanyi WANG ; Bin WANG ; Sidong XIONG ; Xiaoming GAO ; Yucai PENG ; Xia JIN ; Tao ZHU ; Bo YING ; Wei CUN ; Chunlai JIANG ; Jiyun YU ; Ze CHEN ; Jianjun CHEN ; Chunlin XIN
Chinese Journal of Microbiology and Immunology 2024;44(7):565-572
In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.
2.The cellular immune response and protective efficacy against tuberculosis infection of a novel mycobacterium tuberculosis DNA vaccine p846
Nan SU ; Hongmei KONG ; Jiajia WANG ; Jianan HUANG ; Sidong XIONG
The Journal of Practical Medicine 2015;(7):1107-1110
Objective To construct a novel M.tb DNA vaccine (p846) co-expressing mycobacterial triple antigens including Rv3615c, Mtb10.4 and Rv2660c, and evaluate its cellular immune response and protective efficacy against tuberculosis infection in BALB/c mice. Methods We constructed the p846 by using the cloning technology. The 6- to -8-week old female BALB/c mice were randomly divided into 4 groups: p846, pcDNA3.1, PBS and the BCG group. All mice were administrated intramuscularly with 50 μg recombinant plasmids at 0, 2, 4, 6 week. A single dose of BCG was injected subcutaneously in the BCG group. Two weeks after the final immunization, 10 mice in each group were used for cell proliferation, ELISPOT and FCM assay, BCG challenge experiment and HE staining of lung were performed at 4, 6 weeks later, respectively. Results The p846 vaccine could effectively induce the specific T cell proliferation(P < 0.001) and increase the numbers of IFN-γ+T cells(P <0.001), compared with those in the PBS group and the vector conreol group. The mouse lung tissue presented very mild lung inflammation in the p846 group, compared with other groups. Conclusion Vaccine p846 could not only induce strong cellular immune response, but also efficiently protect BALB/c mice against M.tb infection.
3.C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA.
Weijuan ZHANG ; Yanxing CAI ; Wei XU ; Sidong XIONG
Protein & Cell 2011;2(8):672-679
C-reactive protein (CRP), an acute-phase protein with an ability to bind to nuclear antigen, has been reported to regulate cytokine secretion and modulate immune responses. We previously reported that activated syngeneic lymphocyte-derived apoptotic DNA (apopDNA) could induce macrophage activation and contribute to the initiation and progression of lupus nephritis. It is reasonable to hypothesize that CRP might regulate apopDNA-induced macrophage activation. Herein, CRP was shown to promote macrophage-mediated apopDNA uptake by binding to apopDNA (CRP/apopDNA complex). Notably, CRP/apopDNA treatment inhibited the production of inflammatory cytokines and chemokines by macrophages which could be induced by apopDNA alone. Further coculture and transwell studies revealed that CRP/apopDNA-induced macrophages prohibited apopDNA-induced macrophage activation in an IL-10 dependent manner. These results provide insight into the potential mechanism of CRP regulatory activity in macrophage activation induced by apopDNA in the context of lupus nephritis and other autoimmune diseases.
Animals
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C-Reactive Protein
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metabolism
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pharmacology
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Cell Line, Tumor
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DNA
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metabolism
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pharmacology
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Enzyme-Linked Immunosorbent Assay
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Female
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Lupus Erythematosus, Systemic
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metabolism
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Lupus Nephritis
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metabolism
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Macrophage Activation
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drug effects
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physiology
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Mice
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Mice, Inbred BALB C
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Protein Binding
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Real-Time Polymerase Chain Reaction
4.Mechanism of enhanced viral-myocarditis-prophylactic effect of a novel coxsackievirus B3 mucosal vaccine by LTN adjuvant
Yan YUE ; Wei XU ; Sidong XIONG
Chinese Journal of Microbiology and Immunology 2010;30(6):541-545
Objective To explore the mechanism of lymphotactin(LTN) to exert mucosal adjuvant activity. Methods Complexes of chitosan-pVP1 and chitosan-pLTN were seperately prepared by co-cojugation method, then 50μg(DNA) of each complex was administered intranasally to male BALB/c mice 4times biweekly. Two weeks after the final immunization, mice were challenged with 3LD50 CVB3 to cause viral myocarditis, heart histopathological changes were examined 7 days later. Meanwhile, T cell immune responses, DC percentage and its membrane CD86 expression were monitored in spleen, mesenteric lymph node(MLN) and cervical lymph node(CLN). Results Co-immunizaiton with LTN remarkbly alleviated CVB3-induced cardial injury. This improvement was accompanied with enhanced T cell proliferation and IFN-γ-secreting ability, increased DC frequency and membrane CD86 expression both in spleen and mucosal draining lymph nodes( MLN, CLN). Conclusion LTN exerts its mucosal adjuvant function in augmenting specific T cell immune responses systemically and mucosally via DC enrichment in spleen, MLN and CLN and up-regulation of DC maturation.
5.Significance of CCL20 expression in liver biopsies of chronic hepatitis B patients
Xianan SHAO ; Sidong XIONG ; Wei XU ; Fuhua YUAN ; Ruibin LI ; Yong WANG ; Zhihe CHEN ; Changjiang XU
Chinese Journal of Laboratory Medicine 2008;31(8):864-867
Objective To observe the correlation of histologicalactivity(HAI) of chronic hepatitis B (CHB) with CCL20 expression, and to investigate the impact of CCL20 expression in CHB infection. Methods On the basis of established competitive quantitative RT-PCR with an internal standard, the expression of the CCL20 in the hepatocytes in different infected patterns of HBV infected cells and liver biopsies were quantified and at the same time its correlation to HAI were explored. Results In the cell levels, the expression quantity of CCL20 in control cells (HepG2), persistent HBV infected hepatocytes( HepG2. 2. 15) are (2. 65 ± 0. 02) pg/106 cells, ( 1.22± 0. 04) pg/106 cells, respectively. There were significantly differences between them ( t = 39. 66, P < 0. 01 ). The expression of CCL20 was enhanced in hepatocytes stimulated by PMA but their expression pauern was not changed. Moreover, CCL20 expression in liver biopsies with CHB was (3.54 ± 0. 65 ) pg/20 mg and CCL20 expression in control groups was ( 8. 74±0. 56) pg/20 mg. The expression of CCL20 between two groups was different (t =30. 09,P <0. 01 ) and correlation lied in between HAI and CCL20 expression in liver biopsies of CHB patients ( r = 0. 675, P =0. 023 ). Conclusion CCL20 expression was down-regulated and it was correlated to HAI of liver biopsies in CHB patients.
6.Expression of Th1/Th2 Cytokines in Early Syphilitic Lesions and Its Relationship with the Sero-conversion of RPR Test in Patients with Syphilis
Pingyu ZHOU ; Sidong XIONG ; Chunlin YAN ; Jinhua XU ; Kanghuang LIAO
Chinese Journal of Dermatology 2003;0(12):-
Objective To investigate the expression of Th1/Th2 cytoki nes in early symptomatic syphilitic lesions and its relationship with the sero-c onversion of RPR test in patients with syphilis. Methods The expression of Th1/Th2 cytokines in lesions from 30 patients with early symptomatic syphilis was i mmunohistochemically detected with ABC method. The serum titers of RPR test in t hese patients were measured in 1, 3, 6, 9 and 12 months after routine benzathine penicillin treatment. Results Among 10 cases of primary syphilis, the express ion of both Th1 and Th2 cytokines in the lesions was found in 9 cases, while onl y Th1 cytokine expression was observed in the remainder case; and the sero-conve rsion of RPR test occurred in all 10 cases during the follow-up period. Among 20 cases of secondary syphilis, Th1/Th2 cytokines expressed in the lesions in 16 c ases, and only Th2 cytokines expressed in 4 cases; and the sero-conversion of RP R test was found in 12 cases during the follow-up period. The expression of Th1 cytokines in early syphilitic lesions was positively correlated with the sero-co nversion of RPR test. The higher the expression of IFN- the more likely the s ero-conversion of RPR test. Conclusion The early activation and persistence of the expression of Th1 cytokines may play an important role in the clearance of pathogens.
7.Dynamics of Liver Granuloma and the Relative Changes of Th1/Th2 Cytokine Levels in Mice Infected with Schistosoma Japonicum
Chaoming XIA ; Wei GONG ; Wei LUO ; Weifang ZHOU ; Yunhe LI ; Xiliang ZHA ; Sidong XIONG
Fudan University Journal of Medical Sciences 2001;28(1):39-41,46
Purpose To oberve the dynamics of liver granuloma and the relative changes of Thl/Th2cytokine levels in mice infected with Schistosoma japonicum, and investigate the role of Th1/Th2 in S.japontcum granuloma formation and regulation. Methods Liver granuloma measurement were performedby histological examination and the ELISA were used for the quantitative determination of IL-2, IFNr andIL-4 in murine serum and spleen lymphocyte culture medium at 0,4,6,8,10 and 12 wk after infection.Results At 6 wk liver granuloma formation appeared and at 8 wk liver granuloma peaked. After 12 wk livergranuhoma diminished obviously. Meanwhile, at 4 - 6 wk IL-2, IFNr and IL-4 began to rise, at 8 wk thelevels of Th1 cytokines IL-2 and IFNγ peaked and then declined, and at 8 wk the levels of Th2 cytokines IL-4 were rapidly enhanced and increased obviously with a prolongation of the infection duration.Conclusions The Th1cytokines IL-2 and IFNγ were correlated well with S. japonicum granulomaformation and vigour, and the Th2 cytokines IL-4 might play an important role in down-regulating egggranuloma reaction at chronic schistosomiasis by inhibiting the Th1cytokines.
8.Advances in research of the relationship between ectopic hCG and malignant tumor
China Oncology 2001;0(03):-
Ectopic human chorionic gonadotrophin (hCG) is an autocrine hormone expressed by most malignant tumor cells. Increasing data recently showed that the expression pattern and biological properties of ectopic hCG was significantly different from that of the normal hCG secreted by trophoblastic cells. Evidence from different research groups strongly indicated that there was a direct relationship between the expression of ectopic hCG and the development of malignant tumor. Ectopic hCG may play a key role in regulation of tumor growth,metastasis and immune tolerance versus malignant tumor. The advances in the research of the molecular biologic characteristics and functions of ectopic hCG are reviewed and evaluated. [
9.Study on the inhibition of allogeneic transplantation rejection by the B7 antisense peptide
Jin CHEN ; Sidong XIONG ; Ruihua ZHANG ; Al ET
Chinese Journal of Immunology 2001;0(07):-
95%,WT= 1 271 6 .Lymphoproliferation reaction of the splenocytes derived from BALB/C mice was inhibited by stimulating with the antisense peptide pre treatment of allogeneic splenic cells and cardiac cells of C57 mice.The inhibition rates up to 38 4% and 36 6%.Pre treatment of allogeneic cardiac grafts resulted in prolonging the survival of cardiac transplantation 5 4 days more than the control group(n=6,P
10.RADIATION INDUCED PROGRESSIVE DECREASING IN THE EXPRESSION OF REVERSE TRANSCRIPTASE GENE OF hEST2 AND TELOMERASE ACTIVITY
Hanneng ZHU ; Sidong XIONG ; Wenying CHENG
Chinese Medical Sciences Journal 2001;16(2):63-66
Objectives. In order to identify the relationship between telomerase and the biological effect of radiation injury,and investigate the role of human telomerase catalytic subunit gene (hEST2) reverse transcriptase(RT) segment in the expression of telomerase activity. Methods. Tumor HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60Co ray irradiation at RNA level and protein level. Quantitative PCR and Northern blotting were used to determine the expression of hEST2 RT segment that encodes seven motifs of the human telomeres, a PCR based telomeric repeat amplification protocol (TRAP)was used to assay telomerase activity after exposure to radiation. Results. Both of telomerase activity and the expression hEST2 RT segment were decreased with increasing dosage of radiation. In addition, testing the expression of motifs domain is similar to the measurement of telomerase activity. Conclusion. The detection of the hEST2 RT segment by Northern blotting and quantitative PCR are new methods for testing telomerase activity. Furthermore, radiation can cause a dose dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation.

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