Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T...Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.展开更多
Objective The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody ...Objective The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies.Methods Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations.Results HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%–6.93%. Patients who were admitted to the liver disease-related departments(aOR =10.76;95% CI, 10.27–11.28), Internal Medicine(aOR = 2.87;95% CI, 2.75–3.00), and Department of Surgery(aOR = 1.95;95% CI, 1.87–2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older(aOR = 2.74;95% CI,2.69–2.80), testing in infetious disease hospitals(aOR = 2.33;95% CI, 2.26–2.40) and secondary hospitals(aOR = 1.72;95% CI, 1.69–1.75). Patients in sentinel hospitals of the Northeast(aOR = 12.75;95% CI,12.40–13.11), the Central(aOR = 1.65;95% CI, 1.61–1.70), and the West(aOR = 1.78;95% CI, 1.73–1.83)China had higher HCV prevalence than those who were in the Eastern coastal area. Conclusion Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.展开更多
African swine fever virus(ASFV)is a lethal pathogen that causes severe threats to the global swine industry and it has already had catastrophic socio-economic effects.To date,no licensed prophylactic vaccine exists.Li...African swine fever virus(ASFV)is a lethal pathogen that causes severe threats to the global swine industry and it has already had catastrophic socio-economic effects.To date,no licensed prophylactic vaccine exists.Limited knowledge exists about the major immunogens of ASFV and the epitope mapping of the key antigens.As such,there is a considerable requirement to understand the functional monoclonal antibodies(mAbs)and the epitope mapping may be of utmost importance in our understanding of immune responses and designing improved vaccines,therapeutics,and diagnostics.In this study,we generated an ASFV antibody phage-display library from ASFV convalescent swine PBMCs,further screened a specific ASFV major capsid protein(p72)single-chain antibody and fused with an IgG Fc fragment(scFv-83-Fc),which is a specific recognition antibody against ASFV Pig/HLJ/2018 strain.Using the scFv-83-Fc mAb,we selected a conserved epitope peptide(221MTGYKH226)of p72 retrieved from a phage-displayed random peptide library.Moreover,flow cytometry and cell uptake experiments demonstrated that the epitope peptide can significantly promote BMDCs maturation in vitro and could be effectively uptaken by DCs,which indicated its potential application in vaccine and diagnostic reagent development.Overall,this study provided a valuable platform for identifying targets for ASFV vaccine development,as well as to facilitate the optimization design of subunit vaccine and diagnostic reagents.展开更多
The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodi...The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.展开更多
BACKGROUND A case of neuromyelitis optica spectrum disorder(NMOSD)with positive cerebrospinal fluid(CSF)anti-aquaporin-4 antibody(AQP4-IgG)and anti-glial fibrillary acidic protein IgG(GFAP-IgG)at the time of relapse w...BACKGROUND A case of neuromyelitis optica spectrum disorder(NMOSD)with positive cerebrospinal fluid(CSF)anti-aquaporin-4 antibody(AQP4-IgG)and anti-glial fibrillary acidic protein IgG(GFAP-IgG)at the time of relapse was reported.The exact roles of GFAP-IgG in NMOSD are not fully understood and are the subject of ongoing research.This study revealed the possible connection between GFAPIgG and the occurrence or development of diseases.CASE SUMMARY A 19-year-old woman was admitted to the hospital due to a constellation of symptoms,including dizziness,nausea,and vomiting that commenced 1 year prior,reoccurred 2 mo ago,and were accompanied by visual blurring that also began 2 mo ago.Additionally,she presented with slurred speech and ptosis,both of which emerged 1 mo ago.Notably,her symptoms deteriorated 10 d prior to admission,leading to the onset of arm and leg weakness.During hospitalization,magnetic resonance imaging showed high T2-fluid attenuated inversion recovery signals,and slightly high and equal diffusion-weighted imaging signals.The serum antibody of AQP4-IgG tested positive at a dilution of 1:100.CSF antibody testing showed positive results for GFAP-IgG at a dilution of 1:10 and AQP4-IgG at a dilution of 1:32.Based on these findings,the patient was diagnosed with NMOSD.She received intravenous methylprednisolone at a daily dose of 500 mg for 5 d,followed by a tapering-off period.Afterward,the rate of reduction was gradually slowed down and the timely use of immunosuppressants was implemented.CONCLUSION The CFS was slightly GFAP-IgG-positive during the relapse period,which can aid in the diagnosis and treatment of the disease.展开更多
Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poise...Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production.展开更多
Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of...Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.展开更多
Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight g...Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight gain in growing pigs widespread.An accurate method for detecting L.intracellularis is particularly important for preventing and controlling PPE.Heat shock protein 60(Hsp60)is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms.Thus,the purpose of the current investigation was to produce a novel L.intracellularis Hsp60 monoclonal antibody(mAb)useful for immunodiagnostics.Three hybridomas secreted anti-Hsp60 termed 3E5,4E2,and 9G6 were generated,and the titers of ascitic fluids of 3E5,4E2,9G6 were 1:1024000,1:2048000 and 1:2048000,respectively.The Western blotting analysis demonstrated that recombinant Hsp60(rHsp60)was recognized by mAbs 3E5,4E2 and 9G6.Subsequently,analyses of specificity showed all the mAbs were highly specific to L.intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs,such as Escherichia coli,Salmonella Choleraesuis,Salmonella Typhimurium,and Brachyspira hyodysenteriae.Furthermore,the mAbs were useful for detecting L.intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs.Our research will provide a foundation for the development of immunological diagnostic tests.展开更多
Process analytical technology(PAT) is gaining more interest in the biomanufacturing industry because of its potential to improve operational control and compliance through real-time quality assurance.Currently, biopha...Process analytical technology(PAT) is gaining more interest in the biomanufacturing industry because of its potential to improve operational control and compliance through real-time quality assurance.Currently, biopharmaceutical producers mainly monitor chromatographic processes with ultraviolet/visible(UV/Vis) absorbance. However, this measurement has a very limited correlation with purity and quantity. The current study aims to determine the concentration of monoclonal antibody(mAb) and host cell proteins(HCPs) using a build-in UV/Vis monitoring during Protein A affinity chromatography and to optimize the separation conditions for high purity of mAb and minimizing the HCPs content. The eluate was analyzed through in-line UV/Vis at 280 and 410 nm, representing mAb and HCPs concentration,respectively. Each 0.1 column volume(CV) fraction of UV/Vis chromatogram peak area were calculated,and different separation conditions were then compared. The optimum conditions of mAb separation were found as 12 CV loading, elution at pH 3.5, and starting the collection at 0.5 CV point, resulting in high m Ab recovery of 95.92% and additional removal of 49.98% of HCP comparing with whole elution pool. This study concluded that UV/Vis-based in-line monitoring at 280 and 410 nm showed a high potential to optimize and real-time control Protein A affinity chromatography for mAb purification from HCPs.展开更多
Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the d...Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/b-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knockdown.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/b-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/b-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.展开更多
Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome...Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.展开更多
Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in...Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.展开更多
Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is wide...Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is widely distributed in the develo ping and adult central nervous system,participates in neural regeneration remains poorly unde rstood.In this study,we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral co rtex and striatum.Starting on day 7 after injury,CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days.Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting co rticospinal tra ct fibers in rats with cerebral ischemia,increased the expression of vesicular glutamate transporter 1 and growth-related protein 43,marke rs of the denervated spinal cord synapses,and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum.In addition,CXCR7 antibody increased the expression of CXCR4 in the striatum,increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway,and im proved rat motor function.These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration,synaptogenesis,and myelin regeneration,which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.展开更多
Effective detection of methamphetamine(Met)requires a fast,sensitive,and cheap testing assay.However,commercially available methods require expensive instruments and highly trained operators,which are time-consuming a...Effective detection of methamphetamine(Met)requires a fast,sensitive,and cheap testing assay.However,commercially available methods require expensive instruments and highly trained operators,which are time-consuming and labor-intensive.Herein,an antibody-modified graphene transistor assay is developed for sensitive and minute-level detection of Met in complex environments.The anti-Met probe captured charged targets within 120 s,leading to a p-doping effect near the graphene channel.The limit of detection reaches 50 aM(5.0×10^(-17)M)Met in solution.The graphene transistor would be a valuable tool for Met detection effective prevention of drug abuse.展开更多
Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multi...Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.展开更多
Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in...Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in prophylaxis,calling for the need for drug improvement.Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms.The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments,providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies.A total of 128 sequences were obtained after sequencing 196 memory B cells,and 42 sequences were left after merging extremely similar ones and discarding incomplete ones,followed by homology modeling of the antibody variable region.Thirteen candidate sequences were expressed,of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants.The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.展开更多
Bovine tuberculosis(bTB)is a chronic zoonotic disease that is endemic in China.Current in-vitro tests for bTB are mainly based on blood assays.Collection of samples results in some stress to the sampled cattle and ass...Bovine tuberculosis(bTB)is a chronic zoonotic disease that is endemic in China.Current in-vitro tests for bTB are mainly based on blood assays.Collection of samples results in some stress to the sampled cattle and associated economic losses for the herd owner.This study was designed to investigate the relationship between milk and serum antibody tests for bTB in dairy cows using 85 cows with milk and corresponding blood samples.Totally 4,395 milk samples were used to assesse the apparent(test)prevalence and incidence of bTB using the milk antibody ELISA.The association between levels of bTB milk antibody and milk quality was also evaluated.Milk and serum antibody tests showed a good correlation with a 87.5%(95%CI:61.7%,98.4)positive agreement and 98.7%(95%CI:95.4,99.8)negative agreement.The animal level lactoprevalence ranged from 0.3%(95%CI:0,1.2)to 33.3%(95%CI:26.6,40.6)in different farms and the incidence rate ranged from 0 head/cow-month(95%CI:0,0.02)to 0.04 head/cow-month(95%CI:0.02,0.07).Twenty percent of sampled farms met the criteria for bTB control in China.The prevalence on large-scale farms was lower(p<0.001)than on small farms.The bTB milk antibody levels had a negative correlation with milk yield and a positive correlation with somatic cell count(SCC),milk protein percentage(MPP)and percentage of total solids(TS).According to this research,milk ELISA could be used as a supplement of blood samples to assist in the surveillance for bTB and for alerting control and eradication of bTB.展开更多
BACKGROUND It is not uncommon to develop viral encephalitis.Epidemic Japanese B encephalitis infection combined with contactin-associated protein-like 2(CASPR-2)antibody-positive autoimmune encephalitis has not been r...BACKGROUND It is not uncommon to develop viral encephalitis.Epidemic Japanese B encephalitis infection combined with contactin-associated protein-like 2(CASPR-2)antibody-positive autoimmune encephalitis has not been reported at present.In clinical work,we need to consider more options.CASE SUMMARY A 32-year-old male worker presented with headache,fever and call-unresponsive presentation.Complete cranial magnetic resonance image showed symmetrical abnormal signals in bilateral medial temporal lobe,bilateral thalamus and basal ganglia.Improved lumbar puncture showed that cerebrospinal fluid protein and cell count increased significantly.Viral encephalitis was considered,and the patient's consciousness still increased rapidly after antiviral treatment.Further detection of Cerebrospinal fluid Japanese B encephalitis virus Polymerase Chain Reaction positive,serum autoimmune encephalitis antibody showed CASPR-2 antibody positive(1:320),the patient's condition gradually improved after plasma exchange treatment.3 mo later,the serum CASPR-2 antibody was negative and the patient's condition was stable.CONCLUSION This article reports the world’s first case of Epidemic Japanese B encephalitis infection combined with CASPR-2 antibody-positive autoimmune encephalitis,with a view to raising awareness.展开更多
BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and rela...BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and relapse manifestations have not been reported in myeloperoxidase(MPO)-AAV patients.CASE SUMMARY A 52-year-old woman was admitted to our hospital because of headache.Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria,serum creatinine of 243μmol/L,anti-MPO antibody titer of>400 RU/mL,and positive perinuclearantineutrophil cytoplasmic antibody.Renal biopsy showed pauci-immune crescentic glomerulonephritis.The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality.Therefore,MPO-AAV was diagnosed.Corticosteroids,plasmapheresis,and cyclophosphamide as induction therapy and mycophenolate mofetil(MMF)as maintenance therapy were administered.The patient’s headache disappeared;serum creatinine returned to normal;complete remission of microscopic hematuria and proteinuria was observed.Anti-MPO antibody titer reached normal limits after immunosuppressive treatment.Twenty-five months after stopping the immunosuppressive treatment,the patient relapsed with arthralgia,without neurological or renal involvement.The patient’s arthralgia improved after treatment with prednisone and MMF.CONCLUSION We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement.However,relapse presented with only arthralgia,which was completely different from the initial manifestations.This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission,when clinical manifestations at relapse are different from those at onset.Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.展开更多
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.
文摘Objective The prevalence and related factors of serum anti-HCV in different regions and hospitals have not been studied extensively in China. We used routine screening data to determine the prevalence of HCV antibody in hospital patients, evaluate the epidemic trend of hepatitis C and formulate screening strategies.Methods Patient information and HCV antibody testing results were collected from January 2017 to December 2019 in 77 HCV sentinel hospitals in China. Univariate and multivariate logistic regression was used to determine the characteristics and associations.Results HCV antibody prevalence rates were distinct among patients in different departments, with a range of 0.33%–6.93%. Patients who were admitted to the liver disease-related departments(aOR =10.76;95% CI, 10.27–11.28), Internal Medicine(aOR = 2.87;95% CI, 2.75–3.00), and Department of Surgery(aOR = 1.95;95% CI, 1.87–2.04), were more likely to be tested for HCV antibody positive. HCV antibody prevalence was associated with patients aged 45 years and older(aOR = 2.74;95% CI,2.69–2.80), testing in infetious disease hospitals(aOR = 2.33;95% CI, 2.26–2.40) and secondary hospitals(aOR = 1.72;95% CI, 1.69–1.75). Patients in sentinel hospitals of the Northeast(aOR = 12.75;95% CI,12.40–13.11), the Central(aOR = 1.65;95% CI, 1.61–1.70), and the West(aOR = 1.78;95% CI, 1.73–1.83)China had higher HCV prevalence than those who were in the Eastern coastal area. Conclusion Those who were over 45 years old and saw doctors for liver diseases, and invasive diagnosis and treatment should be referred to HCV antibody testing.
基金supported by the National Natural Science Foundation of China(31941001 and 32002292)the Major Science and Technology Project of Henan Province,China(221100110600)the Natural Science Foundation of Henan Province(202300410199).
文摘African swine fever virus(ASFV)is a lethal pathogen that causes severe threats to the global swine industry and it has already had catastrophic socio-economic effects.To date,no licensed prophylactic vaccine exists.Limited knowledge exists about the major immunogens of ASFV and the epitope mapping of the key antigens.As such,there is a considerable requirement to understand the functional monoclonal antibodies(mAbs)and the epitope mapping may be of utmost importance in our understanding of immune responses and designing improved vaccines,therapeutics,and diagnostics.In this study,we generated an ASFV antibody phage-display library from ASFV convalescent swine PBMCs,further screened a specific ASFV major capsid protein(p72)single-chain antibody and fused with an IgG Fc fragment(scFv-83-Fc),which is a specific recognition antibody against ASFV Pig/HLJ/2018 strain.Using the scFv-83-Fc mAb,we selected a conserved epitope peptide(221MTGYKH226)of p72 retrieved from a phage-displayed random peptide library.Moreover,flow cytometry and cell uptake experiments demonstrated that the epitope peptide can significantly promote BMDCs maturation in vitro and could be effectively uptaken by DCs,which indicated its potential application in vaccine and diagnostic reagent development.Overall,this study provided a valuable platform for identifying targets for ASFV vaccine development,as well as to facilitate the optimization design of subunit vaccine and diagnostic reagents.
文摘The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.
基金Hospital Level Project of Jiaxing First Hospital,No.2022-YB-034.
文摘BACKGROUND A case of neuromyelitis optica spectrum disorder(NMOSD)with positive cerebrospinal fluid(CSF)anti-aquaporin-4 antibody(AQP4-IgG)and anti-glial fibrillary acidic protein IgG(GFAP-IgG)at the time of relapse was reported.The exact roles of GFAP-IgG in NMOSD are not fully understood and are the subject of ongoing research.This study revealed the possible connection between GFAPIgG and the occurrence or development of diseases.CASE SUMMARY A 19-year-old woman was admitted to the hospital due to a constellation of symptoms,including dizziness,nausea,and vomiting that commenced 1 year prior,reoccurred 2 mo ago,and were accompanied by visual blurring that also began 2 mo ago.Additionally,she presented with slurred speech and ptosis,both of which emerged 1 mo ago.Notably,her symptoms deteriorated 10 d prior to admission,leading to the onset of arm and leg weakness.During hospitalization,magnetic resonance imaging showed high T2-fluid attenuated inversion recovery signals,and slightly high and equal diffusion-weighted imaging signals.The serum antibody of AQP4-IgG tested positive at a dilution of 1:100.CSF antibody testing showed positive results for GFAP-IgG at a dilution of 1:10 and AQP4-IgG at a dilution of 1:32.Based on these findings,the patient was diagnosed with NMOSD.She received intravenous methylprednisolone at a daily dose of 500 mg for 5 d,followed by a tapering-off period.Afterward,the rate of reduction was gradually slowed down and the timely use of immunosuppressants was implemented.CONCLUSION The CFS was slightly GFAP-IgG-positive during the relapse period,which can aid in the diagnosis and treatment of the disease.
文摘Antibody-drug conjugates (ADCs) are pioneering biologics that merge antibodies’ specificity with small molecules’ potency. With a handful of FDA-approved ADCs in the market and many under development, ADCs are poised to revolutionize therapeutics. This paper examines the complexities of ADC production, emphasizing the importance of process characterization and the pivotal role of supply chain characteristics, safety requirements, and Contract Manufacturing Organizations (CMOs) with proficiency. The swift transition of antibody-drug conjugate (ADC) programs from early to advanced clinical stages underscores the urgency for quick and efficient commercial launch preparation. This article delves into strategies to hasten commercial readiness, supply chain strategy, the significance of partnering with adept contract development and manufacturing organizations (CDMOs), and the challenges of ADC production.
文摘Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.
基金supported by the National Key Research and Development Program of China(2021YFD1800400)the National Natural Science Foundation of China(31872480)+1 种基金the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(19)2020)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(PAPD).
文摘Porcine proliferative enteropathy(PPE),an important infectious disease in pig production caused by an obligate intracellular bacterium Lawsonia intracellularis,is commonly associated with diarrhea and reduced weight gain in growing pigs widespread.An accurate method for detecting L.intracellularis is particularly important for preventing and controlling PPE.Heat shock protein 60(Hsp60)is an immunodominant bacterial antigen found in all eukaryotic and prokaryotic organisms.Thus,the purpose of the current investigation was to produce a novel L.intracellularis Hsp60 monoclonal antibody(mAb)useful for immunodiagnostics.Three hybridomas secreted anti-Hsp60 termed 3E5,4E2,and 9G6 were generated,and the titers of ascitic fluids of 3E5,4E2,9G6 were 1:1024000,1:2048000 and 1:2048000,respectively.The Western blotting analysis demonstrated that recombinant Hsp60(rHsp60)was recognized by mAbs 3E5,4E2 and 9G6.Subsequently,analyses of specificity showed all the mAbs were highly specific to L.intracellularis while could not significantly react with other enteric bacteria commonly found in the ileum of pigs,such as Escherichia coli,Salmonella Choleraesuis,Salmonella Typhimurium,and Brachyspira hyodysenteriae.Furthermore,the mAbs were useful for detecting L.intracellularis in the infected monolayer cells and histological sections of the ileum from PPE-affected pigs.Our research will provide a foundation for the development of immunological diagnostic tests.
基金supported by the National Key Research & Development Program of China (2021YFE0113300)the National Natural Science Foundation of China (22078286 and 21878263)+1 种基金Zhejiang Universitythe Talent-Introduction Program of China for the Postdoctoral Researcher for the financial support。
文摘Process analytical technology(PAT) is gaining more interest in the biomanufacturing industry because of its potential to improve operational control and compliance through real-time quality assurance.Currently, biopharmaceutical producers mainly monitor chromatographic processes with ultraviolet/visible(UV/Vis) absorbance. However, this measurement has a very limited correlation with purity and quantity. The current study aims to determine the concentration of monoclonal antibody(mAb) and host cell proteins(HCPs) using a build-in UV/Vis monitoring during Protein A affinity chromatography and to optimize the separation conditions for high purity of mAb and minimizing the HCPs content. The eluate was analyzed through in-line UV/Vis at 280 and 410 nm, representing mAb and HCPs concentration,respectively. Each 0.1 column volume(CV) fraction of UV/Vis chromatogram peak area were calculated,and different separation conditions were then compared. The optimum conditions of mAb separation were found as 12 CV loading, elution at pH 3.5, and starting the collection at 0.5 CV point, resulting in high m Ab recovery of 95.92% and additional removal of 49.98% of HCP comparing with whole elution pool. This study concluded that UV/Vis-based in-line monitoring at 280 and 410 nm showed a high potential to optimize and real-time control Protein A affinity chromatography for mAb purification from HCPs.
基金supported by the National Basic Research Program of China(Grant No.:2015CB553701)the National Science and Technology Major Project,China(Grant No.:2019ZX09732001).
文摘Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/b-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knockdown.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/b-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/b-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.
基金National Natural Science Foundation of China,No.U1604181Henan Province Key R&D and Promotion Special Project (Science and Technology Tackle),No.212102310834+1 种基金Henan Medical Education Research Project,No.Wjlx2020531the Joint project of Medical Science and Technology Research Program of Henan Province,No.LHGJ20190078 (all to JW)。
文摘Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.
基金This work was supported by the National Key Research&Development Program of China(No.2021YFC2701402).
文摘Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.
基金supported by the National Natural Science Foundation of China,Nos.81401002 (to SSZ),81801 053 (to XQZ)。
文摘Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4(CXCR4) have been shown to regulate neural regeneration after stroke.Howeve r,whether stromal cell-derived factor-1 receptor CXCR7,which is widely distributed in the develo ping and adult central nervous system,participates in neural regeneration remains poorly unde rstood.In this study,we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral co rtex and striatum.Starting on day 7 after injury,CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days.Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting co rticospinal tra ct fibers in rats with cerebral ischemia,increased the expression of vesicular glutamate transporter 1 and growth-related protein 43,marke rs of the denervated spinal cord synapses,and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum.In addition,CXCR7 antibody increased the expression of CXCR4 in the striatum,increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway,and im proved rat motor function.These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration,synaptogenesis,and myelin regeneration,which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.
基金funded by the National Key R&D Program of China(No.2021YFE0201400)the National Natural Science Foundation of China(Nos.51773041,61890940,22066011)+3 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB30000000)the Department of Education of Jiangxi Province(No.GJJ211105)Jiangxi Science&Technology Normal University(No.2021QNBJRC002)State Key Laboratory of Molecular Engineering of Polymers.
文摘Effective detection of methamphetamine(Met)requires a fast,sensitive,and cheap testing assay.However,commercially available methods require expensive instruments and highly trained operators,which are time-consuming and labor-intensive.Herein,an antibody-modified graphene transistor assay is developed for sensitive and minute-level detection of Met in complex environments.The anti-Met probe captured charged targets within 120 s,leading to a p-doping effect near the graphene channel.The limit of detection reaches 50 aM(5.0×10^(-17)M)Met in solution.The graphene transistor would be a valuable tool for Met detection effective prevention of drug abuse.
基金the Ethics Committee of Tongji Hospital,Huazhong University of Science and Technology,China(TJ-IRB20191012).
文摘Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.
基金supported by the Jiangsu Provincial Key Research and Development Program (Grant No.BE2020616)the National Key R&D Program of China (Grant No.2018YFC1200603)+1 种基金the National Science and Technology Major Project (Grant No.2019SWAQ05-5-4)Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University.
文摘Although vaccines have been developed,mutations of SARS-CoV-2,especially the dominant B.1.617.2(delta)and B.1.529(omicron)strains with more than 30 mutations on their spike protein,have caused a significant decline in prophylaxis,calling for the need for drug improvement.Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms.The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments,providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies.A total of 128 sequences were obtained after sequencing 196 memory B cells,and 42 sequences were left after merging extremely similar ones and discarding incomplete ones,followed by homology modeling of the antibody variable region.Thirteen candidate sequences were expressed,of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants.The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.
基金the Natural Science Foundation of China(U21A20259)National Key Research and Development Program of Ningxia Hui Autonomous Region(2021BEF02028)+1 种基金the Natural Science Foundation of Hubei Province(2021CFA016)China Agriculture Research System of MOF and MARA and Basic and technical innovation team for prevention and control of bovine disease.
文摘Bovine tuberculosis(bTB)is a chronic zoonotic disease that is endemic in China.Current in-vitro tests for bTB are mainly based on blood assays.Collection of samples results in some stress to the sampled cattle and associated economic losses for the herd owner.This study was designed to investigate the relationship between milk and serum antibody tests for bTB in dairy cows using 85 cows with milk and corresponding blood samples.Totally 4,395 milk samples were used to assesse the apparent(test)prevalence and incidence of bTB using the milk antibody ELISA.The association between levels of bTB milk antibody and milk quality was also evaluated.Milk and serum antibody tests showed a good correlation with a 87.5%(95%CI:61.7%,98.4)positive agreement and 98.7%(95%CI:95.4,99.8)negative agreement.The animal level lactoprevalence ranged from 0.3%(95%CI:0,1.2)to 33.3%(95%CI:26.6,40.6)in different farms and the incidence rate ranged from 0 head/cow-month(95%CI:0,0.02)to 0.04 head/cow-month(95%CI:0.02,0.07).Twenty percent of sampled farms met the criteria for bTB control in China.The prevalence on large-scale farms was lower(p<0.001)than on small farms.The bTB milk antibody levels had a negative correlation with milk yield and a positive correlation with somatic cell count(SCC),milk protein percentage(MPP)and percentage of total solids(TS).According to this research,milk ELISA could be used as a supplement of blood samples to assist in the surveillance for bTB and for alerting control and eradication of bTB.
文摘BACKGROUND It is not uncommon to develop viral encephalitis.Epidemic Japanese B encephalitis infection combined with contactin-associated protein-like 2(CASPR-2)antibody-positive autoimmune encephalitis has not been reported at present.In clinical work,we need to consider more options.CASE SUMMARY A 32-year-old male worker presented with headache,fever and call-unresponsive presentation.Complete cranial magnetic resonance image showed symmetrical abnormal signals in bilateral medial temporal lobe,bilateral thalamus and basal ganglia.Improved lumbar puncture showed that cerebrospinal fluid protein and cell count increased significantly.Viral encephalitis was considered,and the patient's consciousness still increased rapidly after antiviral treatment.Further detection of Cerebrospinal fluid Japanese B encephalitis virus Polymerase Chain Reaction positive,serum autoimmune encephalitis antibody showed CASPR-2 antibody positive(1:320),the patient's condition gradually improved after plasma exchange treatment.3 mo later,the serum CASPR-2 antibody was negative and the patient's condition was stable.CONCLUSION This article reports the world’s first case of Epidemic Japanese B encephalitis infection combined with CASPR-2 antibody-positive autoimmune encephalitis,with a view to raising awareness.
文摘BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and relapse manifestations have not been reported in myeloperoxidase(MPO)-AAV patients.CASE SUMMARY A 52-year-old woman was admitted to our hospital because of headache.Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria,serum creatinine of 243μmol/L,anti-MPO antibody titer of>400 RU/mL,and positive perinuclearantineutrophil cytoplasmic antibody.Renal biopsy showed pauci-immune crescentic glomerulonephritis.The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality.Therefore,MPO-AAV was diagnosed.Corticosteroids,plasmapheresis,and cyclophosphamide as induction therapy and mycophenolate mofetil(MMF)as maintenance therapy were administered.The patient’s headache disappeared;serum creatinine returned to normal;complete remission of microscopic hematuria and proteinuria was observed.Anti-MPO antibody titer reached normal limits after immunosuppressive treatment.Twenty-five months after stopping the immunosuppressive treatment,the patient relapsed with arthralgia,without neurological or renal involvement.The patient’s arthralgia improved after treatment with prednisone and MMF.CONCLUSION We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement.However,relapse presented with only arthralgia,which was completely different from the initial manifestations.This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission,when clinical manifestations at relapse are different from those at onset.Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.
