Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection,the protection period of vaccination and the possibility of bui...Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection,the protection period of vaccination and the possibility of building an active herd immunity.This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan.A total of404 serum samples were obtained over six months from hospitalization to convalescence.Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays(CLIA).All patients were positive for the anti-SARS-Co V-2 Ig M/Ig G at the onset of COVID-19 symptoms,and the Ig G antibody persisted in all the patients during the convalescence.However,only approximately 25%of patients can detect the Ig M antibodies,Ig M against N protein(NIg M)and receptor binding domain of S protein(RBD-Ig M)at the 27 th week.The titers of Ig M,N-Ig M and RBD-Ig M reduced to 16.7%,17.6%and 15.2%of their peak values respectively.In contrast,the titers of Ig G,N-Ig G and RBD-Ig G peaked at 4–5 th week and reduced to 85.9%,62.6%and 87.2%of their peak values respectively at the end of observation.Dynamic behavior of antibodies and their correlation in age,gender and severity groups were investigated.In general,the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients.Only a few patients with antibody reducing to an undetectable level which needs further attention.The humoral immune response against SARS-Co V-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.展开更多
Objective This study aimed to investigate the effects of Montanide ISA-720 and Naloxone(NLX)in Hepatitis B surface antigen(HBsAg)vaccine formulation on cytokine and long-lasting antibody responses.Methods First,the HB...Objective This study aimed to investigate the effects of Montanide ISA-720 and Naloxone(NLX)in Hepatitis B surface antigen(HBsAg)vaccine formulation on cytokine and long-lasting antibody responses.Methods First,the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10mg/kg.The experimental mice were immunized three times at a 2-week interval,and then IL-4,IL-2,TNF-α,and IFN-γcytokines;long-lasting IgG antibody responses 220 days after the last shot;and IgG1/IgG2a isotypes were assessed by ELISA.Results The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups,whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses.In addition,NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio.Moreover,HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses,and NLX in Alum-and MON720-based vaccines induced long-lasting antibody responses.Conclusion NLX in Alum-based vaccine decreased IL-4 cytokine response,increased IL-2/IL-4 cytokine ratio,and improved long-lasting humoral immune responses in both vaccine formulations.Therefore,the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.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
Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug ...Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance,critical limitations such as inherent cytotoxicity,poor solubility,and instability in aqueous solution remain significant challenges requiring systematic optimization.In this study,we synthesized water-soluble molecular iron-oxo clusters(MIC)with excellent biosafety and stability of aqueous solution.Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models,a critical validation given sepsis'etiology as a life-threatening infection mediated systemic inflammatory syndrome.MIC combats bacteria by enhancing humoral immune responsiveness.MIC significantly improved the survival rate,reduced bacterial burden,stabilized body temperature,and modulated cytokine profiles in mice with sepsis.Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation,and mitigates mitochondrial damage and apoptosis in B cells,suggesting its role in modulating cellular metabolism.RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity,inflammatory responses,and metabolic adaptation.These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis,providing innovative strategies to improve recovery from this life-threatening condition.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 break immune tolerance to prion （PrP） proteins using DNA vaccines.Methods Four different human prion DNA vaccine candidates were constructed based on the pcDNA3.1 vector：PrP‐WT expressing wild‐type P...Objective To break immune tolerance to prion （PrP） proteins using DNA vaccines.Methods Four different human prion DNA vaccine candidates were constructed based on the pcDNA3.1 vector：PrP‐WT expressing wild‐type PrP,Ubiq‐PrP expressing PrP fused to ubiquitin,PrP‐LII expressing PrP fused to the lysosomal integral membrane protein type II lysosome‐targeting signal,and PrP‐ER expressing PrP locating the ER.Using a prime‐boost strategy,three‐doses of DNA vaccine were injected intramuscularly into Balb/c mice,followed by two doses of PrP protein.Two weeks after the last immunization,sera and spleens were collected and PrP‐specific humoral and cellular immune responses evaluated by ELISA and ELISPOT tests.Results Higher levels of serum PrP antibodies were detected in mice vaccinated using the strategy of DNA priming followed by protein boosting.Of these,WT‐PrP,Ubiq‐PrP,and PrP‐LII induced significantly higher humoral responses.ELISPOT tests showed markedly increased numbers of IFN‐γ‐secreting T cells in mice vaccinated using the strategy of DNA priming followed by protein boosting after stimulation with recombinant PrP23‐90 and PrP23‐231.PrP‐ER inducedthe strongest T‐cell response.Conclusion Prion vaccines can break tolerance to PrP proteins and induce PrP‐specific humoral and cellular immune responses.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
Toxoplasmosis is a cosmopolitan antrhropozoonosis widespread in mammals and birds. Normally asymptomatic in the subject health, it can have serious consequences for the fetus in the first trimester of pregnancy in the...Toxoplasmosis is a cosmopolitan antrhropozoonosis widespread in mammals and birds. Normally asymptomatic in the subject health, it can have serious consequences for the fetus in the first trimester of pregnancy in the pregnant woman. It is in this context that we propose to assess the immune response to T. gondii in pregnant women in Bangui. This was a retrospective analytical study that consulted the records of pregnant women received in prenatal consultations at the Bangui Community Hospital Maternity ward from January 2019 to December 2019. Socio-demographic and laboratory data (IgM, IgG response to T. gondii) and results of HIV serology were collected from January to June 2021. Chi<sup>2</sup> test was used. A total of 307 pregnant women were analyzed. The average age of the women included was 28 (±6) years. The average parity of the entire sample was 2.18 (±1.93). Toxoplasmosis infectious was 14.65%. Women with a positive IgM response accounted for 17.58% and those with an IgG-positive response for 42.99%. Patients with a positive HIV were 5.86%. Patients aged 20 - 29 had a serological profile suggesting a probable ongoing infection (p = 0.010). The paucipares were more represented with no statistically significant difference (p = 0.23). Pregnant women were not significantly exposed to toxoplasmosis infectious (p = 0.96). Immunized and non-immunized subjects were similarly exposed [OR = 0.97;CI 95% 0.4 = 6 - 2.05]. Toxoplasmosis remains particularly serious during pregnancy. Seroprevalence was significantly higher in the 20 - 24 year age group. Women were similarly exposed depending on whether they were immunized or not. This requires the establishment of a specific prevention program against this disease.展开更多
Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to...Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to assess the immunological response to vaccination in Senegalese hemodialysis patients. Patients and Methods: We conducted a prospective study, in two dialysis centers in Dakar from March 30<sup>th</sup> to August 30<sup>th</sup>, 2021 including patients on hemodialysis for >6 months, vaccinated against SARS-CoV-2 according to the vaccination schedule recommended by WHO. A vaccine response was considered positive when seroconversion was observed after one dose of vaccine. The clinical efficacy of immunization was defined as the absence of new COVID-19 infection in patients who received a complete vaccination. Results: Among the 81 patients included in the study, 7.4% had anti-Spike IgM antibodies before their first vaccination. Seroprevalence of IgM antibodies was 38.3% one month after the first vaccine dose (at M1) and 8.6% one month after the second dose (at M4). Anti-Spike IgG antibodies were present in 40.3% of patients before vaccination, in 90.1% at M1, and in 59.7% at M4. Among patients previously infected with SARS-CoV-2, 10.2% had IgM antibodies at M0, 31.6% at M1, and 10.5% at M4 post-vaccination. Similarly, seroprevalences of IgG antibodies in this subgroup were 31.5%, 61.3%, and 50.0% respectively at M0, M1, and M4 post-vaccination. A comparison of seroconversion rates between M0 and M4 showed significant differences only for IgG in COVID-19 naive patients. Mean duration in dialysis and the existence of previous COVID-19 infection were associated with patients’ vaccinal response after the two doses. Age, gender and the use of immunosuppressive treatment did not influence post-vaccinal antibody production. Conclusion: Vaccination against COVID-19 in Senegalese hemodialysis patients induced a low seroconversion rate but it was well tolerated. Moreover, the induced protection was neither strong nor durable, particularly in patients with longer duration in dialysis.展开更多
BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporalit...BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporality of reinfection,provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and consequently helps in global public health and vaccination strategy.Among the patients who became infected with SARS-CoV-2,the majority who did not progress to death were those who developed the mild COVID-19,so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G(IgG)in mild cases of COVID-19.METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction(RT-qPCR)-positive volunteers from the municipality of Toledo/Paraná/Brazil,underwent two distinct serological tests,enzyme-linked immunosorbent assay,and detection of anti-nucleocapsid IgG.Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021.All assays were performed in duplicate and the manufacturers'recommendations were strictly followed.The data were statistically analyzed using multiple logistic regression;the variables were selected by applying the P<0.05 criterion.RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo.The time periods when the highest number of participants with detectable IgG was observed were 1,2 and 3 mo.It was observed that 9.42%of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57%were also IgG negative at less than 1 mo.At 5 mo,3.14%of volunteers were IgG negative,and at 6 or 7 mo,1 volunteer(0.52%)had no detectable IgG.During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study,no statistical significance was observed for any association analyzed.Moreover,considering the age category between 31 and 59 years as the exposed group,the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older,showing that in both age categories there was no association between the pair of variables analyzed.Regarding chronic disease,the exposure group consisted of the participants without any comorbidity,so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.CONCLUSION A temporal pattern of IgG response was not observed,but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.展开更多
AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were s...AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.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
Background We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B 11, which mimics an ovarian carcinoma associated antigen OC166-9 and whose corresponding monoclonal antibody...Background We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B 11, which mimics an ovarian carcinoma associated antigen OC166-9 and whose corresponding monoclonal antibody is COC166-9 （Abl）. In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment （scFv）/human granulocyte macrophage colony-stimulating factor （hGM-CSF） and 6B 1 lscFv in BALB/c mice. Methods The fusion protein 6B 11 scFv/hGM-CSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-CSE BALB/c mice were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively. Results The fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F（ab）2＇ and was also biologically active as measured by proliferation of human GM-CSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and 6BllScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11 scFv/hGM-CSF compared with the 6B11 scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week. Conclusion The fusion protein 6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11 scFv/hGM-CSF for active immunotherapy of ovarian cancer.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
The H9N2 subtype avian influenza virus(AIV)inactivated vaccine has been used extensively in poultry farms,but it often fails to stimulate a sufficiently high immune response in poultry in the field,although it works w...The H9N2 subtype avian influenza virus(AIV)inactivated vaccine has been used extensively in poultry farms,but it often fails to stimulate a sufficiently high immune response in poultry in the field,although it works well in laboratory experiments;hence,the virus still causes economic damage every year and poses a potential threat to public health.Based on surveillance data collected in the field,we found that broilers with high levels of maternal-derived antibodies(MDAs)against H9N2 virus did not produce high levels of antibodies after vaccination with a commercial H9N2 inactivated vaccine.In contrast,specific pathogen-free(SPF)chickens without MDAs responded efficiently to that vaccination.When MDAs were mimicked by administering passively transferred antibodies(PTAs)into SPF chickens in the laboratory,similar results were observed:H9N2-specific PTAs inhibited humoral immunity against the H9N2 inactivated vaccine,suggesting that H9N2-specific MDAs might hinder the generation of antibodies when H9N2 inactivated vaccine was used.After challenge with homologous H9N2 virus,the virus was detected in oropharyngeal swabs of the vaccinated and unvaccinated chickens with PTAs but not in the vaccinated chickens without PTAs,indicating that H9N2-specific MDAs were indeed one of the reasons for H9N2 inactivated vaccine failure in the field.When different titers of PTAs were used to mimic MDAs in SPF chickens,high(HI=12 log2)and medium(HI=log 9 log2)titers of PTAs reduced the generation of H9N2-specific antibodies after the first vaccination,but a booster dose would induce a high and faster humoral immune response even of PTA interference.This study strongly suggested that high or medium titers of MDAs might explain H9N2 inactivated vaccine failure in the field.展开更多
Epstein-Barr virus(EBV),the first identified human tumor virus,is implicated in various human malignancies,infectious mononucleosis,and more recently,multiple sclerosis.Prophylactic vaccines have the potential to effe...Epstein-Barr virus(EBV),the first identified human tumor virus,is implicated in various human malignancies,infectious mononucleosis,and more recently,multiple sclerosis.Prophylactic vaccines have the potential to effectively prevent EBV infection.Glycoprotein B(gB)serves as the fusogen and plays a pivotal role in the virus entry process,making it a critical target for EBV vaccine development.Surface membrane proteins of enveloped viruses serve as native conformational antigens,making them susceptible to immune recognition.Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context.In this study,we employed a truncated design for gB proteins,observing that these truncated gB proteins prompted a substantial release of extracellular vesicles(EVs)in insect cells.We verified that EVs exhibited abundant gB proteins,displaying the typical virus particle morphology and extracellular vesicle characteristics.gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice.Moreover,the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity.Consequently,gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.展开更多
In this paper, we consider two nonlinear models for viral infection with humoraL immu- nity. The first model contains four compartments; uninfected target cells, actively infected cells, free virus particles and B cel...In this paper, we consider two nonlinear models for viral infection with humoraL immu- nity. The first model contains four compartments; uninfected target cells, actively infected cells, free virus particles and B cells. The second model is a modification of the first one by including the latently infected cells. The incidence rate, removal rate of infected cells, production rate of viruses and the latent-to-active conversion rate are given by more general nonlinear functions. We have established a set of conditions on these general functions and determined two threshold parameters for each model which are sufficient to determine the global dynamics of the models. The global asymptotic stability of all equilibria of the models has been proven by using Lyapunov theory and applying LaSalle＇s invariance principle. We have performed some numerical simulations for the models with specific forms of the general functions. We have shown that, the numerical results are consistent with the theoretical results.展开更多
Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We...Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2020YFC0861100 and 2020YFC0000)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB29050100)+2 种基金the Key Technology Development Program of Shenzhen(Grant No.JSGG20200225153042494)the Youth Innovation Promotion Association of CAS(Grant No.2014308)the Interdisciplinary Innovation Team of CAS。
文摘Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection,the protection period of vaccination and the possibility of building an active herd immunity.This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan.A total of404 serum samples were obtained over six months from hospitalization to convalescence.Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays(CLIA).All patients were positive for the anti-SARS-Co V-2 Ig M/Ig G at the onset of COVID-19 symptoms,and the Ig G antibody persisted in all the patients during the convalescence.However,only approximately 25%of patients can detect the Ig M antibodies,Ig M against N protein(NIg M)and receptor binding domain of S protein(RBD-Ig M)at the 27 th week.The titers of Ig M,N-Ig M and RBD-Ig M reduced to 16.7%,17.6%and 15.2%of their peak values respectively.In contrast,the titers of Ig G,N-Ig G and RBD-Ig G peaked at 4–5 th week and reduced to 85.9%,62.6%and 87.2%of their peak values respectively at the end of observation.Dynamic behavior of antibodies and their correlation in age,gender and severity groups were investigated.In general,the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients.Only a few patients with antibody reducing to an undetectable level which needs further attention.The humoral immune response against SARS-Co V-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.
基金supported by a grant from the Deputy of Research and Technology,Health Ministry of Iran[Grant no.642]partially by a grant from the Pasteur Institute of Iran。
文摘Objective This study aimed to investigate the effects of Montanide ISA-720 and Naloxone(NLX)in Hepatitis B surface antigen(HBsAg)vaccine formulation on cytokine and long-lasting antibody responses.Methods First,the HBsAg was formulated in Montanide ISA-720 adjuvant and Naloxone at 5 and 10mg/kg.The experimental mice were immunized three times at a 2-week interval,and then IL-4,IL-2,TNF-α,and IFN-γcytokines;long-lasting IgG antibody responses 220 days after the last shot;and IgG1/IgG2a isotypes were assessed by ELISA.Results The HBsAg-Alum group exhibited the highest IL-4 cytokine response among the experimental groups,whereas NLX in HBsAg-MON720 vaccine formulation did not affect cytokine responses.In addition,NLX in Alum-based vaccine suppressed IL-4 cytokine response and increased the IL-2/IL-4 cytokine ratio.Moreover,HBsAg-MON720 was more potent than HBsAg-Alum in the induction of antibody responses,and NLX in Alum-and MON720-based vaccines induced long-lasting antibody responses.Conclusion NLX in Alum-based vaccine decreased IL-4 cytokine response,increased IL-2/IL-4 cytokine ratio,and improved long-lasting humoral immune responses in both vaccine formulations.Therefore,the adjuvant activity of NLX in the vaccine formulation depends on the type of adjuvant and the nature of the antigen in the vaccine formulation.
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the generous supported by the National Key R&D Program of China(No.2023YFC2413100)the National Natural Science Foundation of China(Nos.22322102,21871042 and 21471028)+1 种基金the Fundamental Research Funds for the Central Universities-Excellent Youth Team Program(No.2412023YQ001)the Natural Science Foundation of Jilin Province(Nos.YDZJ202401550ZYTS,20200201083JC)。
文摘Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance,critical limitations such as inherent cytotoxicity,poor solubility,and instability in aqueous solution remain significant challenges requiring systematic optimization.In this study,we synthesized water-soluble molecular iron-oxo clusters(MIC)with excellent biosafety and stability of aqueous solution.Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models,a critical validation given sepsis'etiology as a life-threatening infection mediated systemic inflammatory syndrome.MIC combats bacteria by enhancing humoral immune responsiveness.MIC significantly improved the survival rate,reduced bacterial burden,stabilized body temperature,and modulated cytokine profiles in mice with sepsis.Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation,and mitigates mitochondrial damage and apoptosis in B cells,suggesting its role in modulating cellular metabolism.RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity,inflammatory responses,and metabolic adaptation.These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis,providing innovative strategies to improve recovery from this life-threatening condition.
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 Chinese National Natural Science Foundation Grants 30771914 and 30800975Institution Technique R&D Grant (2008EG150300)+2 种基金National Basic Research Program of China (973 Program) (2007CB310505)China Mega-Project for Infectious Disease (2009ZX10004‐101, 2008ZX10004‐001, and 2008ZX10004‐002)the SKLID Development Grant (2008SKLID102 and 2008SKLID202)
文摘Objective To break immune tolerance to prion （PrP） proteins using DNA vaccines.Methods Four different human prion DNA vaccine candidates were constructed based on the pcDNA3.1 vector：PrP‐WT expressing wild‐type PrP,Ubiq‐PrP expressing PrP fused to ubiquitin,PrP‐LII expressing PrP fused to the lysosomal integral membrane protein type II lysosome‐targeting signal,and PrP‐ER expressing PrP locating the ER.Using a prime‐boost strategy,three‐doses of DNA vaccine were injected intramuscularly into Balb/c mice,followed by two doses of PrP protein.Two weeks after the last immunization,sera and spleens were collected and PrP‐specific humoral and cellular immune responses evaluated by ELISA and ELISPOT tests.Results Higher levels of serum PrP antibodies were detected in mice vaccinated using the strategy of DNA priming followed by protein boosting.Of these,WT‐PrP,Ubiq‐PrP,and PrP‐LII induced significantly higher humoral responses.ELISPOT tests showed markedly increased numbers of IFN‐γ‐secreting T cells in mice vaccinated using the strategy of DNA priming followed by protein boosting after stimulation with recombinant PrP23‐90 and PrP23‐231.PrP‐ER inducedthe strongest T‐cell response.Conclusion Prion vaccines can break tolerance to PrP proteins and induce PrP‐specific humoral and cellular immune responses.
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.
文摘Toxoplasmosis is a cosmopolitan antrhropozoonosis widespread in mammals and birds. Normally asymptomatic in the subject health, it can have serious consequences for the fetus in the first trimester of pregnancy in the pregnant woman. It is in this context that we propose to assess the immune response to T. gondii in pregnant women in Bangui. This was a retrospective analytical study that consulted the records of pregnant women received in prenatal consultations at the Bangui Community Hospital Maternity ward from January 2019 to December 2019. Socio-demographic and laboratory data (IgM, IgG response to T. gondii) and results of HIV serology were collected from January to June 2021. Chi<sup>2</sup> test was used. A total of 307 pregnant women were analyzed. The average age of the women included was 28 (±6) years. The average parity of the entire sample was 2.18 (±1.93). Toxoplasmosis infectious was 14.65%. Women with a positive IgM response accounted for 17.58% and those with an IgG-positive response for 42.99%. Patients with a positive HIV were 5.86%. Patients aged 20 - 29 had a serological profile suggesting a probable ongoing infection (p = 0.010). The paucipares were more represented with no statistically significant difference (p = 0.23). Pregnant women were not significantly exposed to toxoplasmosis infectious (p = 0.96). Immunized and non-immunized subjects were similarly exposed [OR = 0.97;CI 95% 0.4 = 6 - 2.05]. Toxoplasmosis remains particularly serious during pregnancy. Seroprevalence was significantly higher in the 20 - 24 year age group. Women were similarly exposed depending on whether they were immunized or not. This requires the establishment of a specific prevention program against this disease.
文摘Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to assess the immunological response to vaccination in Senegalese hemodialysis patients. Patients and Methods: We conducted a prospective study, in two dialysis centers in Dakar from March 30<sup>th</sup> to August 30<sup>th</sup>, 2021 including patients on hemodialysis for >6 months, vaccinated against SARS-CoV-2 according to the vaccination schedule recommended by WHO. A vaccine response was considered positive when seroconversion was observed after one dose of vaccine. The clinical efficacy of immunization was defined as the absence of new COVID-19 infection in patients who received a complete vaccination. Results: Among the 81 patients included in the study, 7.4% had anti-Spike IgM antibodies before their first vaccination. Seroprevalence of IgM antibodies was 38.3% one month after the first vaccine dose (at M1) and 8.6% one month after the second dose (at M4). Anti-Spike IgG antibodies were present in 40.3% of patients before vaccination, in 90.1% at M1, and in 59.7% at M4. Among patients previously infected with SARS-CoV-2, 10.2% had IgM antibodies at M0, 31.6% at M1, and 10.5% at M4 post-vaccination. Similarly, seroprevalences of IgG antibodies in this subgroup were 31.5%, 61.3%, and 50.0% respectively at M0, M1, and M4 post-vaccination. A comparison of seroconversion rates between M0 and M4 showed significant differences only for IgG in COVID-19 naive patients. Mean duration in dialysis and the existence of previous COVID-19 infection were associated with patients’ vaccinal response after the two doses. Age, gender and the use of immunosuppressive treatment did not influence post-vaccinal antibody production. Conclusion: Vaccination against COVID-19 in Senegalese hemodialysis patients induced a low seroconversion rate but it was well tolerated. Moreover, the induced protection was neither strong nor durable, particularly in patients with longer duration in dialysis.
文摘BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019(COVID-19)is one of the essential factors to better characterize the immune memory of patients,which allows understanding the temporality of reinfection,provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and consequently helps in global public health and vaccination strategy.Among the patients who became infected with SARS-CoV-2,the majority who did not progress to death were those who developed the mild COVID-19,so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G(IgG)in mild cases of COVID-19.METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction(RT-qPCR)-positive volunteers from the municipality of Toledo/Paraná/Brazil,underwent two distinct serological tests,enzyme-linked immunosorbent assay,and detection of anti-nucleocapsid IgG.Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021.All assays were performed in duplicate and the manufacturers'recommendations were strictly followed.The data were statistically analyzed using multiple logistic regression;the variables were selected by applying the P<0.05 criterion.RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo.The time periods when the highest number of participants with detectable IgG was observed were 1,2 and 3 mo.It was observed that 9.42%of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57%were also IgG negative at less than 1 mo.At 5 mo,3.14%of volunteers were IgG negative,and at 6 or 7 mo,1 volunteer(0.52%)had no detectable IgG.During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study,no statistical significance was observed for any association analyzed.Moreover,considering the age category between 31 and 59 years as the exposed group,the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older,showing that in both age categories there was no association between the pair of variables analyzed.Regarding chronic disease,the exposure group consisted of the participants without any comorbidity,so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.CONCLUSION A temporal pattern of IgG response was not observed,but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.
基金Serum Institute of India, Pune, India and Indian Council for Medical Research (ICMR) New Delhi, India
文摘AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders. METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers. RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response. CONCLUSION: Our findings suggest that unrespon-siveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.
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.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30471959 and 30571940).
文摘Background We have previously developed and characterized a monoclonal anti-idiotype antibody, designated 6B 11, which mimics an ovarian carcinoma associated antigen OC166-9 and whose corresponding monoclonal antibody is COC166-9 （Abl）. In this study, we evaluate the humoral immune responses induced by the fusion protein 6B11 single-chain variable fragment （scFv）/human granulocyte macrophage colony-stimulating factor （hGM-CSF） and 6B 1 lscFv in BALB/c mice. Methods The fusion protein 6B 11 scFv/hGM-CSF was constructed by fusing a recombinant single-chain variable fragment of 6B11scFv to GM-CSE BALB/c mice were administrated by 6B11scFv/hGM-CSF and 6B11scFv, respectively. Results The fusion protein 6B11scFv/hGM-CSF retained binding to the anti-mouse F（ab）2＇ and was also biologically active as measured by proliferation of human GM-CSF dependent cell TF1 in vitro. After immunization with the 6B11scFv/hGM-CSF and 6BllScFv, BALB/c mice showed significantly enhanced Ab3 antibody responses to 6B11 scFv/hGM-CSF compared with the 6B11 scFv alone. The level of Ab3 was the highest after the first week and maintained for five weeks after the last immunization. Another booster was given when the Ab3 titer descended, and it would reach to the high level in a week. Conclusion The fusion protein 6B11scFv/hGM-CSF can induce humoral immunity against ovarian carcinoma in vivo. We also provide the theoretical foundation for the application of the fusion protein 6B11 scFv/hGM-CSF for active immunotherapy of ovarian cancer.
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.
基金This study was supported by grants from the National Key Research and Development Plan(Nos.2016YFD0500204 and 2017YFD0500800)National Natural Science Foundation of China(Nos.31772753,31572543,31700136 and 31702237)+1 种基金Shanghai Municipal Natural Science Foundation(No.17ZR1437400)the Project of the Shanghai Science and Technology Commission(No.17391901700).
文摘The H9N2 subtype avian influenza virus(AIV)inactivated vaccine has been used extensively in poultry farms,but it often fails to stimulate a sufficiently high immune response in poultry in the field,although it works well in laboratory experiments;hence,the virus still causes economic damage every year and poses a potential threat to public health.Based on surveillance data collected in the field,we found that broilers with high levels of maternal-derived antibodies(MDAs)against H9N2 virus did not produce high levels of antibodies after vaccination with a commercial H9N2 inactivated vaccine.In contrast,specific pathogen-free(SPF)chickens without MDAs responded efficiently to that vaccination.When MDAs were mimicked by administering passively transferred antibodies(PTAs)into SPF chickens in the laboratory,similar results were observed:H9N2-specific PTAs inhibited humoral immunity against the H9N2 inactivated vaccine,suggesting that H9N2-specific MDAs might hinder the generation of antibodies when H9N2 inactivated vaccine was used.After challenge with homologous H9N2 virus,the virus was detected in oropharyngeal swabs of the vaccinated and unvaccinated chickens with PTAs but not in the vaccinated chickens without PTAs,indicating that H9N2-specific MDAs were indeed one of the reasons for H9N2 inactivated vaccine failure in the field.When different titers of PTAs were used to mimic MDAs in SPF chickens,high(HI=12 log2)and medium(HI=log 9 log2)titers of PTAs reduced the generation of H9N2-specific antibodies after the first vaccination,but a booster dose would induce a high and faster humoral immune response even of PTA interference.This study strongly suggested that high or medium titers of MDAs might explain H9N2 inactivated vaccine failure in the field.
基金supported by the National Natural Science Foundation of China(82073756).
文摘Epstein-Barr virus(EBV),the first identified human tumor virus,is implicated in various human malignancies,infectious mononucleosis,and more recently,multiple sclerosis.Prophylactic vaccines have the potential to effectively prevent EBV infection.Glycoprotein B(gB)serves as the fusogen and plays a pivotal role in the virus entry process,making it a critical target for EBV vaccine development.Surface membrane proteins of enveloped viruses serve as native conformational antigens,making them susceptible to immune recognition.Utilizing lipid membrane-bound viral antigens is a promising strategy for effective vaccine presentation in this context.In this study,we employed a truncated design for gB proteins,observing that these truncated gB proteins prompted a substantial release of extracellular vesicles(EVs)in insect cells.We verified that EVs exhibited abundant gB proteins,displaying the typical virus particle morphology and extracellular vesicle characteristics.gB EVs demonstrated a more efficient humoral and cellular immune response compared with the gB ectodomain trimer vaccine in mice.Moreover,the antisera induced by the gB EVs vaccine exhibited robust antibody-dependent cytotoxicity.Consequently,gB EVs-based vaccines hold significant potential for preventing EBV infection and offer valuable insights for vaccine design.
文摘In this paper, we consider two nonlinear models for viral infection with humoraL immu- nity. The first model contains four compartments; uninfected target cells, actively infected cells, free virus particles and B cells. The second model is a modification of the first one by including the latently infected cells. The incidence rate, removal rate of infected cells, production rate of viruses and the latent-to-active conversion rate are given by more general nonlinear functions. We have established a set of conditions on these general functions and determined two threshold parameters for each model which are sufficient to determine the global dynamics of the models. The global asymptotic stability of all equilibria of the models has been proven by using Lyapunov theory and applying LaSalle＇s invariance principle. We have performed some numerical simulations for the models with specific forms of the general functions. We have shown that, the numerical results are consistent with the theoretical results.
基金supported by the National Science and Technology Major Project of China(2017ZX10202203-007,2017 ZX10202203-008,2018ZX10302206-003)Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical University and The First batch of key Disciplines On Public Health in Chongqing+1 种基金support of the National Natural Science Foundation of China(81772198)Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0389).
文摘Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.
