[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Meth...[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Methods]A total of 120 one-day old female Hyline brown laying hens were randomly divided into 4 groups,30 hens for each group.The chicks in group 1 were subcutaneously injected with NRTUAs and fed on the diet containing with ABP;the chicks in group 2 were subcutaneously injected with NRTUAs;the chicks in group 3 were subcutaneously injected with equal volume of PBS,and fed on the diet containing with ABP;the chicks in group 4 were subcutaneously injected with equal volume of PBS.The body weight of chicks in each group was counted at the 21^(st),42^(nd),84^(th)and 112^(th)week.During this period,blood samples were collected from chicks in each group at 0,7,14,21,28 and 35 d post immunization against Newcastle disease(ND),and serum was separated to detect the antibody titer of ND.[Results]The combined application of NRTUAs and ABP had no effect on growth of chicks,but promoted the humoral immune response of chicks,significantly improved the ND antibody level of chicks,and could maintain high levels of antibodies in the body for a long time.[Conclusions]The study lays a theoretical foundation for further developing the clinical application of NRTUAs and ABP.展开更多
Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin l...Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.展开更多
The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-2...The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-260 g were divided into five groups and reared in 15 tanks with closed circuiting culture system. The animals were fed 5 diets: basal diet only (control) or supplemented of the basal diet with C. butyricum at doses of 10^3 (CB1), 10^5 (CB2), 10^7 (CB3) or 10^9 (CB4) CFU/g. Compared with the control, the serum phenoloxidase activity was significantly increased by the supplementation (P〈0.05), acid phosphatases activity was increased significantly (P〈0.05) at the doses of 10^9 CFU/g. Serum lysozyme activity peaked at dose of 10^7 CFU/g and in the skin mucus at dose of 10^9 CFU/g. Immunoglobulin M level in the serum and skin mucus was increased except at dose of 10^3 CFU/g (P〈0.05). The growth at the dose of 10^9 CFU/g was higher than that of the control (P〈0.05). It is concluded that supplementation of C. butyricum can mediate the humoral immune responses and improve the growth performance in Miichthys miiuy.展开更多
Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71(SP70) without His-tagged.Then evaluating whether the VLPs could efficiently evoke ...Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71(SP70) without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.展开更多
It is well known that IL4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL4 genemodified tumor vaccine were investigated. The mice were va...It is well known that IL4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL4 genemodified tumor vaccine were investigated. The mice were vaccinated with the IL4 genemodified B16 melanoma cells. Then the proliferative capacity of the splenic lymphocytes, the levels of the antibodies in the murine serum against wildtype B16 cells and the cytotoxicity of the serum to wildtype melanoma cells were detected. Our data showed that the LPSinduced proliferation of the splenic lymphocytes from the mice vaccinated with the IL4 genemodified tumor vaccine increased more significantly than that from mice vaccinated with wildtype tumor vaccine. The cytotoxicity of the serum to wildtype melanoma cells also increased markedly when detected. It was also observed that the number of pulmonary metastases decreased more obviously when the mice were intravenously injected with the mixture of wildtype B16 cells and the serum from the mice vaccinated with the IL4 genemodified B16 cells. Our data demonstrated that humoral immunity might contribute to the antitumor effect of IL4 gene therapy.展开更多
Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid p...Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN-γ cells in CD4 + and CD8 + subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4 + IL4 + cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immune responses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.展开更多
Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with eryt...Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with erythrocyte selenium. Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), and 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P< 0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r= 0.625, P< 0.05), as well as serum IgA (r= 0.462, P< 0.05). In addition, a moderate correlation between the serum IgA and CD4+ percentage (r= 0.130, P> 0.05) was found. Conclusion These results suggested that children in KAA had a comparably low cellular immunity level and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in Kashin-Beck disease patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.展开更多
With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune respon...With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.展开更多
[ Objective] The paper was to study the immune enhancement of ATRA on Newcastle Disease (ND) vaccine. [ Method ] The 1-day-old AA broilers were treated with ATRA at the doses of I and 5 p.mol/kg, respectively. At 7 ...[ Objective] The paper was to study the immune enhancement of ATRA on Newcastle Disease (ND) vaccine. [ Method ] The 1-day-old AA broilers were treated with ATRA at the doses of I and 5 p.mol/kg, respectively. At 7 and 28 days of age, broilers in drug control group, low dose group and high dose group were immunized with ND vaccine by intranasal and eye immunization approach. At 7, 14, 21, 28, 35, 42 and 49 clays of age, seven chickens were randomly se- lected from each group and weighed. The thymus, spleen, bursa of fabrieius and serum were collected for calculating immune organ index of thymus, spleen and bursa of fabricius. The ND specific antibody titers in serum were determined with HI test. [Result] ATRA promoted the growth of thymus, spleen and bursa of fabricius, and improved the immune organ index and ND specific antibody titers of chicks. [ Conclusion] ATRA enhanced the humoral immune response of chicks, and ATRT at the dose of 5 μmol/kg presented more prominent immune enhancement effect on ND vaccine.展开更多
Macleaya cordata extract(MCE)is a potential replacement for antibiotics.In the current study,effects of MCE on the gastrointestinal health and humoral responses of host animals were explored.A total of 30 weanling goa...Macleaya cordata extract(MCE)is a potential replacement for antibiotics.In the current study,effects of MCE on the gastrointestinal health and humoral responses of host animals were explored.A total of 30 weanling goats with similar body weight of 9.15±1.36 kg were randomly allocated into three groups(n=10 per group):control group(CON group,fed with a basal diet),antibiotic group(Abx group,fed with the basal diet supplemented with 0.18 g/d vancomycin and 0.36 g/d neomycin),and MCE group(fed with the basal diet supplemented with 5 g/d MCE),for three weeks.Results showed that antibiotic addition decreased the height and area of rumen papillae,ruminal mucosa Toll-like receptor 8(TLR8),interleukin-8(IL-8)and interleukin-1β(IL-1β)gene relative expression levels and microbial diversity,altered the volatile fatty acid(VFA)profile in the rumen,and increased monocytes amount and CD4+T cells percentage in the peripheral blood(P<0.05)compared to CON group.MCE addition increased the average daily gain,ileal villus height,villus height/crypt depth,and immunoglobulin M(IgM)content in the peripheral blood(P<0.05)compared to the CON.Additionally,MCE addition decreased the proportion of isobutyric acid in the chyme of the ileum(P=0.005)compared to the CON group.These results suggest that antibiotic supplementation may suppress the epithelial state and microbial diversity and fermentation in goats,but stimulate cellular response to maintain the growth performance of goats.MCE administration improved the epithelial state and humoral response to promote the growth performance in goats.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response.Howeve...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response.However,their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood.This study utilized various techniques such as luciferase immunoprecipitation system(LIPS),immunofluorescence assay(IFA),and western blot(WB)to detect accessory protein-specific antibodies in sera of COVID-19 patients.Specific antibodies to proteins 3a,3b,7b,8 and 9c can be detected by LIPS,but only protein 3a antibody was detected by IFA or WB.Antibodies against proteins 3a and 7b were only detected in ICU patients,which may serve as a marker for predicting disease progression.Further,we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a,6,7a,8,and 9b.We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a,6,7a,8,9b and 9c were able to induce measurable antibody productions,but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection.Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response,providing a basis for protein detection assays and their role in pathogenesis.展开更多
As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization...As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV difficult.In this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)vector.Compared to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses.The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of MERS-CoV.Prime-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T cells.In conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S.This study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.展开更多
Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct sig...Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways.However,their clinical application is hindered by uncontrolled systemic inflammatory reactions.Therefore,it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy.In this study,we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes(1V209-Cho-Lip^(+))to mitigate undesired side effects.Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8^(+)T cells.The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip^(+)in tumor vaccines.Following immunization with 1V209-Cho-Lip^(+)+OVA,we observed a pronounced"depot effect"and enhanced trafficking to secondary lymphoid organs.Prophylactic vaccination with 1V209-Cho-Lip^(+)^(+)OVA significantly delays tumor development,prolongs mouse survival,and establishes durable immunity against tumor recurrence.Additionally,1V209-Cho-Lip^(+)+OVA,while used therapeutic tumor vaccine,has demonstrated its efficacy in inhibiting tumor progression,and when combined with anti-PD-1,it further enhances antitumor effects.Therefore,the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.展开更多
Objective To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. Methods ICR mice were exposed to different doses of ...Objective To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells (PFCs) at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma (IFN-?) at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha (TNF-α) at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.展开更多
This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of wood...This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.展开更多
Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental fac...Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.展开更多
Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early...Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.展开更多
A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellul...A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.展开更多
Effects of fucoidan from Laminaria japonica on 2,4 dinitrochlorobenzene induced delayed type hypersensitivity (DTH) reaction and the serum levels of IgG, IgM, complement C3 and C4 were investigated in the present stud...Effects of fucoidan from Laminaria japonica on 2,4 dinitrochlorobenzene induced delayed type hypersensitivity (DTH) reaction and the serum levels of IgG, IgM, complement C3 and C4 were investigated in the present study. Results showed that oral administration of fucoidan at dose of 150 and 300 mg/(kg·d) for 9 days before the hapten challenge significantly inhibited 2,4 dinitrochlorobenzene induced delayed type hypersensitivity reaction; and also inhibited the humoral immunity. Serum C3 and C4 levels were markedly reduced by fucoidan at dose of 150 and 300 mg/kg; and serum IgG and IgM levels were reduced by fucoidan at dose of 300 mg/kg. The inhibitory effects of fucoidan on delayed type hypersensitivity suggested that it may be potential medication for chronic inflammatory diseases in the future.展开更多
BACKGROUND Helicobacter pylori(H.pylori)has been found to be associated with extragastrointestinal diseases,possibly including adverse food reactions(such as food allergy or intolerance).However,there are few studies ...BACKGROUND Helicobacter pylori(H.pylori)has been found to be associated with extragastrointestinal diseases,possibly including adverse food reactions(such as food allergy or intolerance).However,there are few studies on H.pylori and food allergy or intolerance,and the results are inconsistent.Food-specific immunoglobulin(Ig)G has been revealed to be associated with food allergy or intolerance and can be used as a marker to explore the correlation between H.pylori infection and food allergy or intolerance.AIM To explore the relationship between H.pylori infection and food-specific IgG METHODS We retrospectively analyzed the physical examination data of 21822 subjects from February 2014 to December 2018 in this study.H.pylori infection was detected using the 13C urea breath test.Food-specific IgG of eggs,milk and wheat in serum was assessed.Subjects were grouped according to H.pylori positivity,and the positive rates of three kinds of food-specific IgG were compared between the two groups.Multivariable logistic regression analysis was performed to elucidate the association between H.pylori infection and food-specific IgG.RESULTS The total infection rate of H.pylori was 39.3%,and the total food-specific IgGpositive rates of eggs,milk and wheat were 25.2%,9.0%and 4.9%,respectively.The infection rate of H.pylori was higher in males than in females,while the positive rates of food-specific IgG were lower in males than in females.The positive rates of food-specific IgG decreased with age in both males and females.In the H.pylori-positive groups,the positive rates of food-specific IgG of eggs,milk and wheat were all lower than those in the H.pylori-negative groups.Multivariate logistic regression analysis revealed that H.pylori infection was negatively correlated with the food-specific IgG-positive rates of eggs,milk and wheat(odds ratio value of eggs 0.844-0.873,milk 0.741-0.751 and wheat 0.755-0.788,in different models).CONCLUSION H.pylori infection was found to be negatively associated with the food-specific IgG of eggs,milk and wheat in Southwest China.展开更多
基金Supported by National Natural Science Foundation of China(31902277)。
文摘[Objectives]The paper was to study the effects of combined application of nonreplicating Toxoplasma uracil auxotrophs(NRTUAs)and Agaricus blazei Murill polysaccharide(ABP)on growth and humoral immunity of chicks.[Methods]A total of 120 one-day old female Hyline brown laying hens were randomly divided into 4 groups,30 hens for each group.The chicks in group 1 were subcutaneously injected with NRTUAs and fed on the diet containing with ABP;the chicks in group 2 were subcutaneously injected with NRTUAs;the chicks in group 3 were subcutaneously injected with equal volume of PBS,and fed on the diet containing with ABP;the chicks in group 4 were subcutaneously injected with equal volume of PBS.The body weight of chicks in each group was counted at the 21^(st),42^(nd),84^(th)and 112^(th)week.During this period,blood samples were collected from chicks in each group at 0,7,14,21,28 and 35 d post immunization against Newcastle disease(ND),and serum was separated to detect the antibody titer of ND.[Results]The combined application of NRTUAs and ABP had no effect on growth of chicks,but promoted the humoral immune response of chicks,significantly improved the ND antibody level of chicks,and could maintain high levels of antibodies in the body for a long time.[Conclusions]The study lays a theoretical foundation for further developing the clinical application of NRTUAs and ABP.
文摘Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.
基金Project supported by the Bureau of Science and Technology of Zhejiang Province (No. 2004201), China and the Youth Fund of Ningbo City (No. 2004A620008), China
文摘The effects of dietary supplementation with Clostridium butyricum on growth performance and humoral immune response in Miichthys miiuy were evaluated. One hundred and fifty Miichthys miiuy weighing approximately 200-260 g were divided into five groups and reared in 15 tanks with closed circuiting culture system. The animals were fed 5 diets: basal diet only (control) or supplemented of the basal diet with C. butyricum at doses of 10^3 (CB1), 10^5 (CB2), 10^7 (CB3) or 10^9 (CB4) CFU/g. Compared with the control, the serum phenoloxidase activity was significantly increased by the supplementation (P〈0.05), acid phosphatases activity was increased significantly (P〈0.05) at the doses of 10^9 CFU/g. Serum lysozyme activity peaked at dose of 10^7 CFU/g and in the skin mucus at dose of 10^9 CFU/g. Immunoglobulin M level in the serum and skin mucus was increased except at dose of 10^3 CFU/g (P〈0.05). The growth at the dose of 10^9 CFU/g was higher than that of the control (P〈0.05). It is concluded that supplementation of C. butyricum can mediate the humoral immune responses and improve the growth performance in Miichthys miiuy.
基金supported by the National Science-technology Support Plan Projects 'The development of EV71 genetic engineering vaccine'[2008BAI69B02]
文摘Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71(SP70) without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.
文摘It is well known that IL4 plays important roles in the induction of humoral immunity. In the present study, the humoral antitumor responses induced by IL4 genemodified tumor vaccine were investigated. The mice were vaccinated with the IL4 genemodified B16 melanoma cells. Then the proliferative capacity of the splenic lymphocytes, the levels of the antibodies in the murine serum against wildtype B16 cells and the cytotoxicity of the serum to wildtype melanoma cells were detected. Our data showed that the LPSinduced proliferation of the splenic lymphocytes from the mice vaccinated with the IL4 genemodified tumor vaccine increased more significantly than that from mice vaccinated with wildtype tumor vaccine. The cytotoxicity of the serum to wildtype melanoma cells also increased markedly when detected. It was also observed that the number of pulmonary metastases decreased more obviously when the mice were intravenously injected with the mixture of wildtype B16 cells and the serum from the mice vaccinated with the IL4 genemodified B16 cells. Our data demonstrated that humoral immunity might contribute to the antitumor effect of IL4 gene therapy.
文摘Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN-γ cells in CD4 + and CD8 + subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4 + IL4 + cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immune responses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.
基金ThisresearchwassupportedbytheNationalNaturalScienceFoundationofChina(No.39770667),theScience&TechnologyDevelopmentFoundationofShaanxiProvince(No.2001SM82)and china and belgium cooperated study
文摘Objective To study the humoral immunity status and distribution pattern of lymphocyte subgroups of peripheral blood mononuclear cell (PBMC) in patients with Kashin-Beck Disease (KBD), and their relationship with erythrocyte selenium. Methods 23 X-ray diagnosed patients, 22 age- and sex- matched healthy children in KBD affected area (KAA), and 25 in KBD non-affected area (KNAA) were randomly selected. Immunohistochemistry with monoclonal antibodies anti-CD4, anti-CD8, anti-CD20 was conducted to analyze the lymphocyte subsets. Serum IgM, IgA, IgG, Complement C3 and C4 were assayed using rate nephelometry (Array 360 System, USA). The contents of erythrocyte selenium was determined by 2,3-diaminonaphthalene fluorescence assay. Results CD4+ and CD8+ cells percentage in PBMCs and serum IgA were significantly lower in KAA than those in KNAA(P< 0.05). CD20+ percentage in KAA displayed a decreasing trend compared to KNAA, although not statistically significantly. No statistical differences were found in CD4/CD8 ratio, serum IgG, IgM, C3 and C4 levels. Erythrocyte selenium level in KAA still showed a pronounced decrease compared to that in KNAA. Correlation analysis showed that erythrocyte selenium contents had a strong association with the CD4 cell percentage (r= 0.625, P< 0.05), as well as serum IgA (r= 0.462, P< 0.05). In addition, a moderate correlation between the serum IgA and CD4+ percentage (r= 0.130, P> 0.05) was found. Conclusion These results suggested that children in KAA had a comparably low cellular immunity level and their humoral immunity status was also in a state of moderate immune suppression. Of this immune disorder in Kashin-Beck disease patients, selenium deficiency probably played a critical role via affecting the distribution pattern of peripheral blood lymphocyte. Selenium-deficiency and immune impairment maybe both have something to do with the cause-effect chain of KBD.
基金supported by the National Natural Science Foundation of China(U1703118)Natural Science Foundation of Jiangsu Province(No.BK20181364)+6 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.19KJA310003)Scientific Research Foundation of Jiangsu health and Health Committee(No.H2018087)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Jiangsu Shuangchuang ProgramOpen Funds of the State Key Laboratory for Chemo/Biosensing and Chemometrics(2016015)Open project of the National Laboratory of Biomacromolecules(2017kf05)the cooperative project between Southeast University and Nanjing Medical University(2018DN0004)Jiangsu Specially-Appointed Professor project,China。
文摘With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.
基金Supported by Science and Technology Development Fund of Tianjin Agricultural University(2013N09)"Veterinary Biological Technology"Innovation Team Project of Colleges and Universities in Tianjin(TD12-5019)+1 种基金Innovative Team Training Program Fund of Colleges and Universities in Tianjin(TNTD2015015)Development Program Leading Education Reform and Innovation of College Teachers at Tianjin Agricultural University(20171003)
文摘[ Objective] The paper was to study the immune enhancement of ATRA on Newcastle Disease (ND) vaccine. [ Method ] The 1-day-old AA broilers were treated with ATRA at the doses of I and 5 p.mol/kg, respectively. At 7 and 28 days of age, broilers in drug control group, low dose group and high dose group were immunized with ND vaccine by intranasal and eye immunization approach. At 7, 14, 21, 28, 35, 42 and 49 clays of age, seven chickens were randomly se- lected from each group and weighed. The thymus, spleen, bursa of fabrieius and serum were collected for calculating immune organ index of thymus, spleen and bursa of fabricius. The ND specific antibody titers in serum were determined with HI test. [Result] ATRA promoted the growth of thymus, spleen and bursa of fabricius, and improved the immune organ index and ND specific antibody titers of chicks. [ Conclusion] ATRA enhanced the humoral immune response of chicks, and ATRT at the dose of 5 μmol/kg presented more prominent immune enhancement effect on ND vaccine.
基金supported by National Key R&D Program of China (2022YFD1301700)Changsha Munic-ipal Natural Science Foundation (kq2208245)+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences (XDA26040304)Natural Science Foundation of Hunan Province of China (2022JJ10054).
文摘Macleaya cordata extract(MCE)is a potential replacement for antibiotics.In the current study,effects of MCE on the gastrointestinal health and humoral responses of host animals were explored.A total of 30 weanling goats with similar body weight of 9.15±1.36 kg were randomly allocated into three groups(n=10 per group):control group(CON group,fed with a basal diet),antibiotic group(Abx group,fed with the basal diet supplemented with 0.18 g/d vancomycin and 0.36 g/d neomycin),and MCE group(fed with the basal diet supplemented with 5 g/d MCE),for three weeks.Results showed that antibiotic addition decreased the height and area of rumen papillae,ruminal mucosa Toll-like receptor 8(TLR8),interleukin-8(IL-8)and interleukin-1β(IL-1β)gene relative expression levels and microbial diversity,altered the volatile fatty acid(VFA)profile in the rumen,and increased monocytes amount and CD4+T cells percentage in the peripheral blood(P<0.05)compared to CON group.MCE addition increased the average daily gain,ileal villus height,villus height/crypt depth,and immunoglobulin M(IgM)content in the peripheral blood(P<0.05)compared to the CON.Additionally,MCE addition decreased the proportion of isobutyric acid in the chyme of the ileum(P=0.005)compared to the CON group.These results suggest that antibiotic supplementation may suppress the epithelial state and microbial diversity and fermentation in goats,but stimulate cellular response to maintain the growth performance of goats.MCE administration improved the epithelial state and humoral response to promote the growth performance in goats.
基金supported by grants from the National Natural Science Foundation of China(82002127,81971500,82025001,82172240)National Key R&D Program of China(2021YFC2301700,2022YFC2604100)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515020059,2021B1515130005)R&D Program of Guangzhou Laboratory(EKPG21-30-2).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response.However,their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood.This study utilized various techniques such as luciferase immunoprecipitation system(LIPS),immunofluorescence assay(IFA),and western blot(WB)to detect accessory protein-specific antibodies in sera of COVID-19 patients.Specific antibodies to proteins 3a,3b,7b,8 and 9c can be detected by LIPS,but only protein 3a antibody was detected by IFA or WB.Antibodies against proteins 3a and 7b were only detected in ICU patients,which may serve as a marker for predicting disease progression.Further,we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a,6,7a,8,and 9b.We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a,6,7a,8,9b and 9c were able to induce measurable antibody productions,but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection.Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response,providing a basis for protein detection assays and their role in pathogenesis.
基金financially supported by National Nature Science Foundation of China(U20A20362)the Subject of SKLID(2020SKLID102).
文摘As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV difficult.In this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)vector.Compared to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses.The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of MERS-CoV.Prime-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T cells.In conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S.This study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.
基金supported by the National Science Foundation for Excellent Young Scholars(32122052,China)National Natural Science Foundation Regional Innovation and Development(No.U19A2003,China).
文摘Toll-like receptor(TLR)agonists,as promising adjuvants and immunotherapeutic agents,have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways.However,their clinical application is hindered by uncontrolled systemic inflammatory reactions.Therefore,it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy.In this study,we designed lymph node-targeted cholesterolized TLR7 agonist cationic liposomes(1V209-Cho-Lip^(+))to mitigate undesired side effects.Co-delivery of the model antigen OVA and cholesterolized TLR7 agonist facilitated DC maturation through TLR activation while ensuring optimal presentation of the antigen to CD8^(+)T cells.The main aim of the present study is to evaluate the adjuvant effectiveness of 1V209-Cho-Lip^(+)in tumor vaccines.Following immunization with 1V209-Cho-Lip^(+)+OVA,we observed a pronounced"depot effect"and enhanced trafficking to secondary lymphoid organs.Prophylactic vaccination with 1V209-Cho-Lip^(+)^(+)OVA significantly delays tumor development,prolongs mouse survival,and establishes durable immunity against tumor recurrence.Additionally,1V209-Cho-Lip^(+)+OVA,while used therapeutic tumor vaccine,has demonstrated its efficacy in inhibiting tumor progression,and when combined with anti-PD-1,it further enhances antitumor effects.Therefore,the co-delivery of antigen and lymph node-targeted cholesterolized TLR7 agonist shows great promise as a cancer vaccine.
基金the Scientific Research Foundation of Health Bureau of Zhejiang Province (No. 2006c151)
文摘Objective To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells (PFCs) at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma (IFN-?) at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha (TNF-α) at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.
基金Supported by contract N01-AI-05399 to the College of Veterinary Medicine, Cornell University from the National Institute of Allergy and Infectious Diseases. PC and SM also have been supported by contract N01-AI-95390 to the Georgetown University Medical Center, Georgetown University from the National Institute of Allergy and Infectious Diseases
文摘This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.
文摘Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.
基金This work was supported by the financial support of the PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to R.B.The financial support of the PID2019-103899RB-I00(Ministerio de Ciencia e Innovación)Research Project and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid(S2018/NMT-4349)to S.C.are gratefully acknowledged.+3 种基金G.D.acknowledges the financial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de InnovaciónThe FPU predoctoral contract to A.M.-C.is supported by the Spanish Ministerio de Educación,Cultura y Deporte.G.S.-F.is recipient of a predoctoral contract(1193818 N)supported by The Flanders Research Foundation(FWO).M.A.-N.was supported by a contract of the Programa Operativo de Empleo Juvenily la Iniciativa de Empleo Juvenil(YEI)with the participation of the Consejería de Educación,Juventud y Deporte de la Comunidad de Madrid y del Fondo Social EuropeoThe predoctoral contract from the Spanish Ministerio de Economía y Competitividad(BES-2016-076606,E.P.)Talento-Contract from Comunidad de Madrid(2019-T2/IND-15965,R.M.T.-R.)are also gratefully acknowledged.
文摘Colorectal cancer(CRC)is the second leading cause of cancer-related death worldwide.The five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced stages.Autoantibodies against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early diagnosis.Thus,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid biopsy.To that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to CRC.After bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC prognosis.After validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC detection.Taken together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here could be integrated into a point-of-care(POC)device for CRC detection with high diagnostic ability.
基金supported by the State Key Program for Basic Research Grant(2005CB523004)from the Chinese Ministry of Science and Technologythe Knowledge Innovation Program Key Project administered by the Chinese Academy of Sciences(KSCX1-YW-R-07)
文摘A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.
文摘Effects of fucoidan from Laminaria japonica on 2,4 dinitrochlorobenzene induced delayed type hypersensitivity (DTH) reaction and the serum levels of IgG, IgM, complement C3 and C4 were investigated in the present study. Results showed that oral administration of fucoidan at dose of 150 and 300 mg/(kg·d) for 9 days before the hapten challenge significantly inhibited 2,4 dinitrochlorobenzene induced delayed type hypersensitivity reaction; and also inhibited the humoral immunity. Serum C3 and C4 levels were markedly reduced by fucoidan at dose of 150 and 300 mg/kg; and serum IgG and IgM levels were reduced by fucoidan at dose of 300 mg/kg. The inhibitory effects of fucoidan on delayed type hypersensitivity suggested that it may be potential medication for chronic inflammatory diseases in the future.
基金by Key Research and Development Projects of the Ministry of Science and Technology,China,No.2017YFC0113901.
文摘BACKGROUND Helicobacter pylori(H.pylori)has been found to be associated with extragastrointestinal diseases,possibly including adverse food reactions(such as food allergy or intolerance).However,there are few studies on H.pylori and food allergy or intolerance,and the results are inconsistent.Food-specific immunoglobulin(Ig)G has been revealed to be associated with food allergy or intolerance and can be used as a marker to explore the correlation between H.pylori infection and food allergy or intolerance.AIM To explore the relationship between H.pylori infection and food-specific IgG METHODS We retrospectively analyzed the physical examination data of 21822 subjects from February 2014 to December 2018 in this study.H.pylori infection was detected using the 13C urea breath test.Food-specific IgG of eggs,milk and wheat in serum was assessed.Subjects were grouped according to H.pylori positivity,and the positive rates of three kinds of food-specific IgG were compared between the two groups.Multivariable logistic regression analysis was performed to elucidate the association between H.pylori infection and food-specific IgG.RESULTS The total infection rate of H.pylori was 39.3%,and the total food-specific IgGpositive rates of eggs,milk and wheat were 25.2%,9.0%and 4.9%,respectively.The infection rate of H.pylori was higher in males than in females,while the positive rates of food-specific IgG were lower in males than in females.The positive rates of food-specific IgG decreased with age in both males and females.In the H.pylori-positive groups,the positive rates of food-specific IgG of eggs,milk and wheat were all lower than those in the H.pylori-negative groups.Multivariate logistic regression analysis revealed that H.pylori infection was negatively correlated with the food-specific IgG-positive rates of eggs,milk and wheat(odds ratio value of eggs 0.844-0.873,milk 0.741-0.751 and wheat 0.755-0.788,in different models).CONCLUSION H.pylori infection was found to be negatively associated with the food-specific IgG of eggs,milk and wheat in Southwest China.