Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from...Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age,gender,and vaccination profile.Live virus-neutralizing antibodies against five SARS-CoV-2 variants,including WT,Gamma,Beta,Delta,and Omicron BA.1,and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.Results The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection,but mainly increased the antibody level against the WT strain,and the antibody against the Omicron strain was the lowest.The neutralizing antibody level decreased rapidly 6 months after infection.The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.Conclusion Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1.Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza.Thus,T-lymphocytes may play an important role in recovery.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
The ongoing Coronavirus disease 19 pandemic has likely changed the world in ways not seen in the past.Neutralizing antibody(NAb)assays play an important role in the management of the severe acute respiratory syndrome ...The ongoing Coronavirus disease 19 pandemic has likely changed the world in ways not seen in the past.Neutralizing antibody(NAb)assays play an important role in the management of the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)outbreak.Using these tools,we can assess the presence and duration of antibody-mediated protection in naturally infected individuals,screen convalescent plasma preparations for donation,test the efficacy of immunotherapy,and analyze NAb titers and persistence after vaccination to predict vaccine-induced protective effects.This review briefly summarizes the various methods used for the detection of SARS-CoV-2 NAbs and compares their advantages and disadvantages to facilitate their development and clinical application.展开更多
Objective The coronavirus disease 2019(COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody(NAb) responses ...Objective The coronavirus disease 2019(COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody(NAb) responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods In total, 605 serum samples from 125 COVID-19 patients(from January 1 to March 14, 2020)varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.Results NAbs were detectable approximately 10 days post-onset(dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Longterm studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.展开更多
Objective In previous studies, we immunized mice with Ebola recombinant protein vaccine and gene vector vaccine. Both stimulated high levels of humoral immunity. In this work, we constructed a pseudovirus containing E...Objective In previous studies, we immunized mice with Ebola recombinant protein vaccine and gene vector vaccine. Both stimulated high levels of humoral immunity. In this work, we constructed a pseudovirus containing Ebola membrane proteins to verify whether the two immunization strategies can induce neutralizing antibodies in mice. Methods A pseudovirus containing an Ebola virus membrane protein based on the HIV-1 viral gene sequence was constructed and evaluated using a known neutralizing antibody. The titer of the neutralizing antibody in the sera of mice immunized with the recombinant protein and the gene vector vaccine was examined using a neutralization test. Results Ebola pseudovirus was successfully prepared and applied for neutralizing antibody detection. Immunological experiments showed that recombinant protein GP-Fc and gene vaccine pVR-modGP-Fc had good immunogenicity. The titer of the bound antibody in the serum after 8 weeks of immunization in mice was more than 1：105, and the recombinant protein induced greater humoral immunity. The results of the neutralization test based on the Ebola pseudovirus system demonstrated that both vaccines induced production of protective antibodies, while the gene vaccine induced a higher titer of neutralizing antibodies. Conclusion An Ebola pseudovirus detection system was successfully established and used to evaluate two Ebola vaccines. Both produced good immunogenicity. The findings lay the foundation for the development of new Ebola vaccines and screening for neutralizing monoclonal antibodies.展开更多
Smallpox eradication was successful via prophylactic administration of live attenuated vaccinia virus. As a result of the discontinuation of the smallpox immunization program, many individuals are now susceptible to s...Smallpox eradication was successful via prophylactic administration of live attenuated vaccinia virus. As a result of the discontinuation of the smallpox immunization program, many individuals are now susceptible to smallpox virus infection should it be used as a biological weapon. Presently, only individuals at high risk for exposure are required to receive smallpox vaccine, such as laboratory personnel that handle variola/vaccinia virus. This study endeavored to investigate a one-year period of vaccinia virus-specific T cell responses using polychromatic flow cytometry and neutralizing (Nt) antibody responses using plaque reduction neutralization test (PRNT) in individuals receiving primary immunization (n = 5) with ACAM2000<sup>TM</sup> smallpox vaccine. Functional and phenotypic profiles of vaccinia virus-specific T cell responses were characterized. Each single functional measurement {CD107a/b expression, production of interferon g (IFN-g), macrophage inflammatory protein 1b (MIP-1b), interleukin 2 (IL-2), and tumor necrosis factor a (TNF-a)} demonstrated that vaccinia virus-specific CD8<sup>+</sup> T cells were functional at least one time point after vaccination (p ≤ 0.05). However, vaccinia virus-specific CD4<sup>+</sup> T cells were functional only for MIP-1b production (p ≤ 0.05). Vaccinia virus-specific CD8<sup>+</sup> T cells induced in these individuals showed increased polyfunctionality in at least 2 phenotypes relative to pre-vaccination (p ≤ 0.05). Although only three of five individuals (60%) showed positive Nt antibody (titer ≥ 20) at first month after vaccination, all five individuals (100%) demonstrated Nt antibody at 2 months, post-immunization. Interestingly, all vaccinees could retain the Nt antibody for 6 months after primary vaccination. In conclusion, ACAM2000<sup>TM</sup> smallpox vaccine induced both polyfunctional T cell-and Nt antibody-responses in primary immunized individuals.展开更多
Objective To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019(COVID-19)at 6 and 10 months after disease onset.Methods Blood samples were collected at thre...Objective To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019(COVID-19)at 6 and 10 months after disease onset.Methods Blood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed.Results The symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1–2 months post polymerase chain reaction confirmation,respectively.However,neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation.Conclusion Continued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.展开更多
The frequency and the consequences of binding and neutralizing antibodies (BAbs and NAbs) against Interferon beta (IFNbeta) in Turkish multiple sclerosis (MS) patients have not been determined yet, which could differ ...The frequency and the consequences of binding and neutralizing antibodies (BAbs and NAbs) against Interferon beta (IFNbeta) in Turkish multiple sclerosis (MS) patients have not been determined yet, which could differ in such a country which is between Europa and Asia. The aim of the study is to assess the frequency of these antibodies, and to evaluate the impact of NAbs, from the clinical and radiologic aspects in Turkish patients with MS. One hundred and two MS patients were included. BAbs were screened using capture enzyme-linked immunosorbent assay (cELISA), and NAbs were detected via Myxovirus protein A (MxA) messenger RNA (mRNA) induction assay (real-time polymerase chain reaction-PCR) at the beginning and one year later. Relapse rate and expanded disability status scale (EDSS) were used to assess the clinical impact. Gadolinium enhanced lesions and T2 lesion volume were used as magnetic resonance imaging (MRI) parameters. Persistent NAb positivity defines to be positive both at first and then one year later. NAbs were detected in 12.2% (6/49) of IFNbeta-1b treated patients, and in 7.5% (3/40) of IFNbeta-1a SC treated patients, but none of the IFNbeta-1a IM treated patients had detectable NAbs. It was found that the mean relapse rate difference was significantly higher in persistent NAb negative patients (p = 0.024). Persistent NAb positivity had no effect on T2 lesion volume and contrast enhancing lesions. 60% of the persistent NAb positive patients had at least one relapse during one-year of follow-up. On the other hand, 32% of persistent NAb negative patients were detected to have at least one relapse. Data from this study suggest that patients may become unresponsive to IFNbeta therapy even when the frequency of NAbs does not prove to be as high as those in the literature. Nevertheless, one should keep in mind that disease activity is not always equal to NAb positivity.展开更多
The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of t...The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.展开更多
Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or vaccination.Th...Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or vaccination.The rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus strain.Here,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron subvariants.Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing.Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5.Together,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.展开更多
Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 ...Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.展开更多
AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mi...AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody （200 pg）. Sevedty of pancreatitis, organ injury （liver, kidney and lung）, and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS： Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION： Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR展开更多
Middle East respiratory syndrome coronavirus （MERS-CoV）, a member of the Coronavifidae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome ...Middle East respiratory syndrome coronavirus （MERS-CoV）, a member of the Coronavifidae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome （ARDS）, as well as extrapul- monary manifestations. Currently, there are no approved treatment regimens or vaccines for MERS. Here~ we generated recombinant nonvirulent Newcastle disease virus （NDV） LaSota strain expressing MERS-CoV S protein （designated as rLa- MERS-S）, and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-MERS-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-MERS-S induced MERS-CoV neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa- MERS-S may be a potential MERS-CoV veterinary vaccine candidate for camels and other animals affected by MERS.展开更多
The serum samples and corresponding cervical swabs were collected from 50 women with genital warts from Tianjin city, China. The neutralizing antibodies against HPV-16, -18, -58, -45, -6 and -11 in serum samples were ...The serum samples and corresponding cervical swabs were collected from 50 women with genital warts from Tianjin city, China. The neutralizing antibodies against HPV-16, -18, -58, -45, -6 and -11 in serum samples were tested by using pseudovirus-based neutralization assays and HPV DNAs in cervical swabs were also tested by using a typing kit that can detect 21 types of HPV. The results revealed that 36% （18/50） of sera were positive for type-specific neutralizing antibodies with a titer range of 160-2560, of which 22%（11/50）, 12%（6/50）, 10%（5/50）, 4%（2/50）, 4%（2/50） and 2%（1/50） were against HPVs -6, -16, -18, -58, -45 and -1 l, respectively. Additionally, 60% （30/50） of samples were HPV DNA-positive, in which the most common types detected were HPV-68（18%）, HPV-16（14%）, HPV-58（12%）, HPV-33（8%） and HPV-6, HPV-11, HPV-18 and HPV-52 （6% each）. The concordance between HPV DNA and corresponding neutralizing antibodies was 56% （28/50） with a significant difference （P〈0.05）. The full-length sequences of five HPV types （HPV -42, -52, -53, -58 and -68） were determined and exhibited 98%-100% identities with their reported genomes. The present data may have utility for investigating the natural history of HPV infection and promote the development of HPV vaccines.展开更多
AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injecti...AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells(PECs) and the local expression of TGF-β isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA) at various time points.In addition,we investigated the effect of TFG-β-neutralizing antibodies(TGF-β NAb) on subretinal fibrosis development.· RESULTS:TGF-β1 and TGF-β2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5,reaching the peak.TGF-β3 mRNA was not detected in the present study.The result of ELSIA showed that active TGF-β1 and TGF-β2 levels were upregulated to 10-fold approximately,while total TGF-β1 and TGF-β2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with na?觙ve mice at day 5.TGF-β NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7.· CONCLUSION:Our results indicate that TGF-β signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-β inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.·展开更多
Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous vir...Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.展开更多
The World Health Organization （WHO） standard assay for determining antibody level is the rapid fluorescent focus inhibition test （RFFIT） and is used to determine the degree of immunity after vaccination against ra...The World Health Organization （WHO） standard assay for determining antibody level is the rapid fluorescent focus inhibition test （RFFIT） and is used to determine the degree of immunity after vaccination against rabies. To compare the difference in RFFIT results between the laboratories of The National Institute of Infectious Disease in Japan （NIID） and the Chinese Centre for Disease Control （CCDC） as well the influence of the choice of standard serum （STD） for the detection, the two laboratories detection methods were simultaneously manipulated by RFFIT. The reference serums used in NIID and the WHO standard serum used in CCDC were compared in the same RFFIT detection to determine the titer of four sera samples C1, Sl, S2 and S4 in parallel, and the titers of the detected sera samples were calculated using the standard formula for neutralizing antibody titer. No significant difference was found in RFFIT methods from the two laboratories and the RFFIT testing procedures of the two laboratories have good consistency. However, different titers were obtained with the tentative internal standard serum （TI-STD） produced by adjusting to 2.0 IU of WHO standard serum in NIID and the WHO STD. The titer determined with the TI-STD was higher than that determined with WHO STD, This difference appears to be significant and requires further investigation展开更多
The new coronavirus disease(COVID-19)outbreak has challenged us to take unprecedented steps to bring this pandemic under control.In view of the urgency of this situation,convalescent plasma which was used in previous ...The new coronavirus disease(COVID-19)outbreak has challenged us to take unprecedented steps to bring this pandemic under control.In view of the urgency of this situation,convalescent plasma which was used in previous coronavirus outbreaks has emerged as one of the treatment options in this current pandemic.This is mainly due to the fact that convalescent plasma has been studied in a few case series with promising outcomes.In addition,on-going large clinical trials aimed to further evaluate the effectiveness,safety,and optimal dosage,duration and timing of administration of convalescent plasma are indeed revealing a certain level of promising results.Therefore,this article aims to provide an overview of possible mechanisms of actions of convalescent plasma,its benefits and its level of usage safeness by summarizing the existing evidence on the use of convalescent plasma in COVID-19 patients.展开更多
The standard rabies vaccines recommended by WHO include Essen regimen, the Thai Red Cross two-site ID regimen and the eight-site ID regimen, and so on. The present schedules of rabies vaccine are all laborious and tim...The standard rabies vaccines recommended by WHO include Essen regimen, the Thai Red Cross two-site ID regimen and the eight-site ID regimen, and so on. The present schedules of rabies vaccine are all laborious and time consuming. We developed a new rabies vaccine with liposome as adjuvant（LipoRabV） and found that liposome could facilitate the inactivated rabies vaccine（RabV） to induce the more vigorous production of rabies virus neutralizing antibody（RVNA） in BALB/c mice and beagles. We established preliminary pre- and post-exposure prophylaxis schedules for LipoRabV. LipoRabV（0/14） could elicit similar RVNA level as RabV（0/7/28） by pre-exposure prophylaxis schedules in mice and beagles. LipoRabV（0/3/14） could elicit higher RVNA level vs. RabV（0/3/7/14/28） in BALB/c. The data indicate that the three-shot liposome-enhanced rabies vaccine could achieve a higher protection rate（survival rate 56.2%） by post-exposure prophylaxis compared with that of the RabV group（survival rate 40.6%） in mice. The data also indicate that the three-inoculation liposome-enhanced rabies vaccine could achieve a survival rate of 80.0% vs. RabV（70.0%） by post-exposure prophylaxis in beagles. The results show that the immunization schedule for LipoRabV could be preliminarily determined at 0 and 14 d for pre-exposure prophylaxis and at 0, 3 and 14 d for post-exposure prophylaxis.展开更多
Hepatitis C virus (HCV) is a member of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. Th...Hepatitis C virus (HCV) is a member of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antibody-mediated virus neutralization. Following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has been markedly advanced. In this review we summarize recent developments in the molecular biology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.展开更多
基金funded by the Emergency prevention and cure Program of COVID-19[22ZXGBSY00010]Tianjin Medical Key Discipline Project[TJYXZDXK-50A]sponsored by Tianjin Municipal Science and Technology Bureau and Tianjin Municipal Health Commission,respectively.
文摘Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age,gender,and vaccination profile.Live virus-neutralizing antibodies against five SARS-CoV-2 variants,including WT,Gamma,Beta,Delta,and Omicron BA.1,and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.Results The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection,but mainly increased the antibody level against the WT strain,and the antibody against the Omicron strain was the lowest.The neutralizing antibody level decreased rapidly 6 months after infection.The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.Conclusion Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1.Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza.Thus,T-lymphocytes may play an important role in recovery.
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supported by grants from the Applied Basic Research Key Project of Wuhan Municipal Bureau of Science and Technology(2020020601012218)the Fundamental Research Funds for the Central Universities(HUST COVID-19 Rapid Response Call No.2020kfyXGYJ040).
文摘The ongoing Coronavirus disease 19 pandemic has likely changed the world in ways not seen in the past.Neutralizing antibody(NAb)assays play an important role in the management of the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)outbreak.Using these tools,we can assess the presence and duration of antibody-mediated protection in naturally infected individuals,screen convalescent plasma preparations for donation,test the efficacy of immunotherapy,and analyze NAb titers and persistence after vaccination to predict vaccine-induced protective effects.This review briefly summarizes the various methods used for the detection of SARS-CoV-2 NAbs and compares their advantages and disadvantages to facilitate their development and clinical application.
基金the Guangdong Provincial Novel Coronavirus Scientific and Technological Project[2020111107001 and202008040004]the National Key Research and Development Program of China[2020YFC0846900]+1 种基金the Guangzhou Basic Research Program on People’s Livelihood Science and Technology[202002020005]the National Natural Science Foundation of China[82003487 and 82072265]。
文摘Objective The coronavirus disease 2019(COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody(NAb) responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods In total, 605 serum samples from 125 COVID-19 patients(from January 1 to March 14, 2020)varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.Results NAbs were detectable approximately 10 days post-onset(dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Longterm studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
基金supported by National Key R&D Program of China [2017YFC1200503]Emergency research Program on the prevention and control of Ebola hemorrhagic fever [1061400100275]
文摘Objective In previous studies, we immunized mice with Ebola recombinant protein vaccine and gene vector vaccine. Both stimulated high levels of humoral immunity. In this work, we constructed a pseudovirus containing Ebola membrane proteins to verify whether the two immunization strategies can induce neutralizing antibodies in mice. Methods A pseudovirus containing an Ebola virus membrane protein based on the HIV-1 viral gene sequence was constructed and evaluated using a known neutralizing antibody. The titer of the neutralizing antibody in the sera of mice immunized with the recombinant protein and the gene vector vaccine was examined using a neutralization test. Results Ebola pseudovirus was successfully prepared and applied for neutralizing antibody detection. Immunological experiments showed that recombinant protein GP-Fc and gene vaccine pVR-modGP-Fc had good immunogenicity. The titer of the bound antibody in the serum after 8 weeks of immunization in mice was more than 1：105, and the recombinant protein induced greater humoral immunity. The results of the neutralization test based on the Ebola pseudovirus system demonstrated that both vaccines induced production of protective antibodies, while the gene vaccine induced a higher titer of neutralizing antibodies. Conclusion An Ebola pseudovirus detection system was successfully established and used to evaluate two Ebola vaccines. Both produced good immunogenicity. The findings lay the foundation for the development of new Ebola vaccines and screening for neutralizing monoclonal antibodies.
文摘Smallpox eradication was successful via prophylactic administration of live attenuated vaccinia virus. As a result of the discontinuation of the smallpox immunization program, many individuals are now susceptible to smallpox virus infection should it be used as a biological weapon. Presently, only individuals at high risk for exposure are required to receive smallpox vaccine, such as laboratory personnel that handle variola/vaccinia virus. This study endeavored to investigate a one-year period of vaccinia virus-specific T cell responses using polychromatic flow cytometry and neutralizing (Nt) antibody responses using plaque reduction neutralization test (PRNT) in individuals receiving primary immunization (n = 5) with ACAM2000<sup>TM</sup> smallpox vaccine. Functional and phenotypic profiles of vaccinia virus-specific T cell responses were characterized. Each single functional measurement {CD107a/b expression, production of interferon g (IFN-g), macrophage inflammatory protein 1b (MIP-1b), interleukin 2 (IL-2), and tumor necrosis factor a (TNF-a)} demonstrated that vaccinia virus-specific CD8<sup>+</sup> T cells were functional at least one time point after vaccination (p ≤ 0.05). However, vaccinia virus-specific CD4<sup>+</sup> T cells were functional only for MIP-1b production (p ≤ 0.05). Vaccinia virus-specific CD8<sup>+</sup> T cells induced in these individuals showed increased polyfunctionality in at least 2 phenotypes relative to pre-vaccination (p ≤ 0.05). Although only three of five individuals (60%) showed positive Nt antibody (titer ≥ 20) at first month after vaccination, all five individuals (100%) demonstrated Nt antibody at 2 months, post-immunization. Interestingly, all vaccinees could retain the Nt antibody for 6 months after primary vaccination. In conclusion, ACAM2000<sup>TM</sup> smallpox vaccine induced both polyfunctional T cell-and Nt antibody-responses in primary immunized individuals.
基金supported by the National Natural Science Foundation of China[82041027]National Key R&D Program of China[2021ZD0114100,2021ZD0114103]+2 种基金The Capital Health Development and Research of Special[2022-1G-3014]Beijing Science and Technology Planning Project of Beijing Science and Technology Commission[Z211100002521015,Z211100002521019]Cooperation project[2022-jk-cd-009]。
文摘Objective To investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019(COVID-19)at 6 and 10 months after disease onset.Methods Blood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2).Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed.Results The symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1–2 months post polymerase chain reaction confirmation,respectively.However,neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation.Conclusion Continued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.
文摘The frequency and the consequences of binding and neutralizing antibodies (BAbs and NAbs) against Interferon beta (IFNbeta) in Turkish multiple sclerosis (MS) patients have not been determined yet, which could differ in such a country which is between Europa and Asia. The aim of the study is to assess the frequency of these antibodies, and to evaluate the impact of NAbs, from the clinical and radiologic aspects in Turkish patients with MS. One hundred and two MS patients were included. BAbs were screened using capture enzyme-linked immunosorbent assay (cELISA), and NAbs were detected via Myxovirus protein A (MxA) messenger RNA (mRNA) induction assay (real-time polymerase chain reaction-PCR) at the beginning and one year later. Relapse rate and expanded disability status scale (EDSS) were used to assess the clinical impact. Gadolinium enhanced lesions and T2 lesion volume were used as magnetic resonance imaging (MRI) parameters. Persistent NAb positivity defines to be positive both at first and then one year later. NAbs were detected in 12.2% (6/49) of IFNbeta-1b treated patients, and in 7.5% (3/40) of IFNbeta-1a SC treated patients, but none of the IFNbeta-1a IM treated patients had detectable NAbs. It was found that the mean relapse rate difference was significantly higher in persistent NAb negative patients (p = 0.024). Persistent NAb positivity had no effect on T2 lesion volume and contrast enhancing lesions. 60% of the persistent NAb positive patients had at least one relapse during one-year of follow-up. On the other hand, 32% of persistent NAb negative patients were detected to have at least one relapse. Data from this study suggest that patients may become unresponsive to IFNbeta therapy even when the frequency of NAbs does not prove to be as high as those in the literature. Nevertheless, one should keep in mind that disease activity is not always equal to NAb positivity.
基金Deutsche Forschungsgemeinschaft(German Research Foundation)-Projektnummer 215346292[Winkler]Bavarian consortium for research on the pandemic disease COVID-19(FOR-COVID)[Tenbusch].
文摘The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.
基金supported by grants from the National Key Research and Development Program of China (No.2021YFC2301404)the National Natural Science Foundation of China (Nos.81991491,82272305,and 32170942)+4 种基金Fujian Natural Science Foundation (No.2020J06007)the Industry-University-Research Project of Xiamen (No.2022CXY0106)the Fundamental Research Funds for the Central Universities (Nos.20720220006 and 20720220004)National Postdoctoral Science Foundation of China (No.2021M712659)CAMS Innovation Fund for Medical Sciences (No.2019RU022).
文摘Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or vaccination.The rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus strain.Here,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron subvariants.Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing.Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5.Together,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.
基金supported by the Natural Science Foundation of Anhui Province of China,No.1708085MH211(to HWC)the College Top-notch Talent Foundation of Anhui Province of China,No.KJ2018A0207(to HWC)
文摘Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and from the Ministry of Health, Labor and Welfare of Japan
文摘AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody （200 pg）. Sevedty of pancreatitis, organ injury （liver, kidney and lung）, and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS： Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION： Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR
基金support by National Key Technology R&D Program of China (2013BAD12B05)
文摘Middle East respiratory syndrome coronavirus （MERS-CoV）, a member of the Coronavifidae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome （ARDS）, as well as extrapul- monary manifestations. Currently, there are no approved treatment regimens or vaccines for MERS. Here~ we generated recombinant nonvirulent Newcastle disease virus （NDV） LaSota strain expressing MERS-CoV S protein （designated as rLa- MERS-S）, and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-MERS-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-MERS-S induced MERS-CoV neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa- MERS-S may be a potential MERS-CoV veterinary vaccine candidate for camels and other animals affected by MERS.
文摘The serum samples and corresponding cervical swabs were collected from 50 women with genital warts from Tianjin city, China. The neutralizing antibodies against HPV-16, -18, -58, -45, -6 and -11 in serum samples were tested by using pseudovirus-based neutralization assays and HPV DNAs in cervical swabs were also tested by using a typing kit that can detect 21 types of HPV. The results revealed that 36% （18/50） of sera were positive for type-specific neutralizing antibodies with a titer range of 160-2560, of which 22%（11/50）, 12%（6/50）, 10%（5/50）, 4%（2/50）, 4%（2/50） and 2%（1/50） were against HPVs -6, -16, -18, -58, -45 and -1 l, respectively. Additionally, 60% （30/50） of samples were HPV DNA-positive, in which the most common types detected were HPV-68（18%）, HPV-16（14%）, HPV-58（12%）, HPV-33（8%） and HPV-6, HPV-11, HPV-18 and HPV-52 （6% each）. The concordance between HPV DNA and corresponding neutralizing antibodies was 56% （28/50） with a significant difference （P〈0.05）. The full-length sequences of five HPV types （HPV -42, -52, -53, -58 and -68） were determined and exhibited 98%-100% identities with their reported genomes. The present data may have utility for investigating the natural history of HPV infection and promote the development of HPV vaccines.
文摘AIM:To determine the involvement of the transforming growth factor(TGF)-β with the development of experimental subretinal fibrosis in a mouse model.· METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells(PECs) and the local expression of TGF-β isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA) at various time points.In addition,we investigated the effect of TFG-β-neutralizing antibodies(TGF-β NAb) on subretinal fibrosis development.· RESULTS:TGF-β1 and TGF-β2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5,reaching the peak.TGF-β3 mRNA was not detected in the present study.The result of ELSIA showed that active TGF-β1 and TGF-β2 levels were upregulated to 10-fold approximately,while total TGF-β1 and TGF-β2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with na?觙ve mice at day 5.TGF-β NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7.· CONCLUSION:Our results indicate that TGF-β signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-β inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.·
基金Inserm, France Université Louis Pasteur, France+3 种基金the European Union (Virgil Network of Excellence)the DeutscheForschungsgemeinschaft (Ba1417/11-1), Germanythe ANRchair of excellence program and ANRS, FranceInserm "PosteVert" research fellowship in the framework of Inserm EuropeanAssociated Laboratory Inserm U748-Department of Medicine Ⅱ,University of Freiburg, Germany
文摘Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodiesfor control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.
基金Grant from National Institute of Infectious Diseases(NIID)National Department Public Benefit Research Foundation (201103032)
文摘The World Health Organization （WHO） standard assay for determining antibody level is the rapid fluorescent focus inhibition test （RFFIT） and is used to determine the degree of immunity after vaccination against rabies. To compare the difference in RFFIT results between the laboratories of The National Institute of Infectious Disease in Japan （NIID） and the Chinese Centre for Disease Control （CCDC） as well the influence of the choice of standard serum （STD） for the detection, the two laboratories detection methods were simultaneously manipulated by RFFIT. The reference serums used in NIID and the WHO standard serum used in CCDC were compared in the same RFFIT detection to determine the titer of four sera samples C1, Sl, S2 and S4 in parallel, and the titers of the detected sera samples were calculated using the standard formula for neutralizing antibody titer. No significant difference was found in RFFIT methods from the two laboratories and the RFFIT testing procedures of the two laboratories have good consistency. However, different titers were obtained with the tentative internal standard serum （TI-STD） produced by adjusting to 2.0 IU of WHO standard serum in NIID and the WHO STD. The titer determined with the TI-STD was higher than that determined with WHO STD, This difference appears to be significant and requires further investigation
基金financially supported by Taylor’s University Emerging Grant(TRGS/ERFS/2/2018/SBS/016)Monash Global Asia in the 21st Century(GA21)research grants(GA-HW-19-L01&GA-HW-19-S02)Fundamental Research Grant Scheme(FRGS/1/2019/WAB09/MUSM/02/1&FRGS/1/2019/SKK08/TAYLOR/02/2)
文摘The new coronavirus disease(COVID-19)outbreak has challenged us to take unprecedented steps to bring this pandemic under control.In view of the urgency of this situation,convalescent plasma which was used in previous coronavirus outbreaks has emerged as one of the treatment options in this current pandemic.This is mainly due to the fact that convalescent plasma has been studied in a few case series with promising outcomes.In addition,on-going large clinical trials aimed to further evaluate the effectiveness,safety,and optimal dosage,duration and timing of administration of convalescent plasma are indeed revealing a certain level of promising results.Therefore,this article aims to provide an overview of possible mechanisms of actions of convalescent plasma,its benefits and its level of usage safeness by summarizing the existing evidence on the use of convalescent plasma in COVID-19 patients.
基金Supported by the National High-Tech Research and Development Programs of China(No.2006AA02A221)
文摘The standard rabies vaccines recommended by WHO include Essen regimen, the Thai Red Cross two-site ID regimen and the eight-site ID regimen, and so on. The present schedules of rabies vaccine are all laborious and time consuming. We developed a new rabies vaccine with liposome as adjuvant（LipoRabV） and found that liposome could facilitate the inactivated rabies vaccine（RabV） to induce the more vigorous production of rabies virus neutralizing antibody（RVNA） in BALB/c mice and beagles. We established preliminary pre- and post-exposure prophylaxis schedules for LipoRabV. LipoRabV（0/14） could elicit similar RVNA level as RabV（0/7/28） by pre-exposure prophylaxis schedules in mice and beagles. LipoRabV（0/3/14） could elicit higher RVNA level vs. RabV（0/3/7/14/28） in BALB/c. The data indicate that the three-shot liposome-enhanced rabies vaccine could achieve a higher protection rate（survival rate 56.2%） by post-exposure prophylaxis compared with that of the RabV group（survival rate 40.6%） in mice. The data also indicate that the three-inoculation liposome-enhanced rabies vaccine could achieve a survival rate of 80.0% vs. RabV（70.0%） by post-exposure prophylaxis in beagles. The results show that the immunization schedule for LipoRabV could be preliminarily determined at 0 and 14 d for pre-exposure prophylaxis and at 0, 3 and 14 d for post-exposure prophylaxis.
文摘Hepatitis C virus (HCV) is a member of the Flaviviridae family and causes acute and chronic hepatitis. Chronic HCV infection may result in severe liver damage including liver cirrhosis and hepatocellular carcinoma. The liver is the primary target organ of HCV, and the hepatocyte is its primary target cell. Attachment of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between the virus and the target cell that is required for successful entry into the cell and initiation of infection. This step is an important determinant of tissue tropism and pathogenesis; it thus represents a major target for antiviral host cell responses, such as antibody-mediated virus neutralization. Following the development of novel cell culture models for HCV infection our understanding of the HCV entry process and mechanisms of virus neutralization has been markedly advanced. In this review we summarize recent developments in the molecular biology of viral entry and its impact on pathogenesis of HCV infection, development of novel preventive and therapeutic antiviral strategies.
