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
Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical ...Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.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
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
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
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
Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immun...Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.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
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 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
Japanese encephalitis(JE),a vector-borne disease caused by the Japanese encephalitis virus(JEV),remains a major public health concern in South and Southeast Asia[1].JEV,a Flaviviridae family virus,is primarily transmi...Japanese encephalitis(JE),a vector-borne disease caused by the Japanese encephalitis virus(JEV),remains a major public health concern in South and Southeast Asia[1].JEV,a Flaviviridae family virus,is primarily transmitted by Culex mosquitoes,especially the Culex vishnui subgroup,which breeds extensively in rice fields[1].Birds(Ardeidae family)act as natural reservoirs,while pigs serve as amplifying hosts,and humans are incidental hosts[1].展开更多
Porcine epidemic diarrhea(PED),caused by porcine epidemic diarrhea virus(PEDV),can induce 80–100%mortality in newborn piglets;therefore,specific and rapid detection methods are important for the prevention of this vi...Porcine epidemic diarrhea(PED),caused by porcine epidemic diarrhea virus(PEDV),can induce 80–100%mortality in newborn piglets;therefore,specific and rapid detection methods are important for the prevention of this viral infection.In particular,methods for detecting neutralizing antibodies(nAbs)can be used to evaluate the immunization effect of PEDV vaccines.The spike protein of PEDV(PEDV-S)has been universally used as an antigen to develop immunoassays to detect nAbs.Nanobodies(Nbs)offer advantages such as ease of genetic engineering and low production costs,making them promising for diagnostic applications.In this study,PEDV-S was expressed via the baculovirus system and was used as an antigen to immunize Bactrian camels.A total of 10 Nbs against PEDV-S were first screened and expressed as fusion proteins with horseradish peroxidase(HRP)in HEK293T cells.A Nb-HRP fusion protein named PEDV-S-Nb13-HRP was subsequently selected and used as a probe for developing a competitive enzyme-linked immunosorbent assay(cELISA)to detect anti-PEDV nAbs.Optimization assays identified 80 ng/well of PEDV-S as the optimal coating antigen concentration.The optimal dilution of PEDV-S-Nb13-HRP was 1:200,and the optimal serum dilution was 1:10.The cutoff value of cELISA was determined as 28.1%,demonstrating high specificity,repeatability,stability,and good agreement rates with two commercial ELISA kits(93.6%)and a serum neutralization test(96.34%).Additionally,the results of the detection of IgA antibodies in oral and milk samples from sows were in good agreement with those of the IDEXX PEDV IgA kit.These results demonstrate that the cELISA is a reliable and cost-effective method for detecting anti-PEDV nAbs.展开更多
In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Boju...In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Bojude,Nigeria.A total of 200 blood samples were collected from pregnant women between February and April 2022.Using the updated CDC guidelines for the diagnosis of ZIKV infections,including ELISA and microneutralization test(MNT),we found that 16.5%of participants were positive for ZIKV IgM,10%were positive for IgG,and 23%had nAb in their serum.Among the 46 ZIKV nAb-positive women,52.2%and 10.9%were recent and previous ZIKV infections,respectively,while 6.5%had previous DENV infections.Although no recent DENV infection was detected,recent and previous ZIKV/DENV co-infections were 13.0%and 17.4%,respectively.Two participants had recent secondary ZIKV infections,while 39.1%had prolonged lifelong immunity.Recent ZIKV infection rates were significantly higher among sexually active females aged 20–29 years than other age groups,with the highest risk observed in the first trimester of pregnancy.In addition,the grand-multiparous women are at higher risk of ZIKV infections than other categories.Monotypic recent,secondary and past ZIKV infections,as well as DENV and ZIKV co-infections,were detected in both the asymptomatic and symptomatic pregnant women.These findings highlight that ZIKV infection is prevalent among pregnant women in Nigeria and underscore the associated risk factors,providing evidence-based information on the burden of ZIKV infections in DENV-endemic region.展开更多
COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to ...COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients.Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected.The median age of the studied cohort was59.83±12.94 years.All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to112 days PIS.Peripheral lymphocytes counts were normal.The ratios of interferon gamma(IFN-c)-secreting cells to total CD4^(+)and CD8^(+)cells were normal as 24.68%±9.60%and 66.41%±14.87%respectively.However,the number of IFNc-secreting NK cells diminished(58.03%±11.78%).All patients presented detectable IgG,which positively correlated with mild neutralizing activity(Mean value neutralisation antibodies titers=157.2,P=0.05).No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS,and the cytopathic effect was lacking.But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages.Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions.In conclusion,decreased IFN-c production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence.Further,low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARSCoV-2 infection.展开更多
Eight strains of nervous necrosis virus （NNV） isolated in Vietnam were used to detect the pathogenicity and immune response in sea bass （SB）. All strains induced cytopathic effect in SB cell line, complete destruc...Eight strains of nervous necrosis virus （NNV） isolated in Vietnam were used to detect the pathogenicity and immune response in sea bass （SB）. All strains induced cytopathic effect in SB cell line, complete destruction of monolayer of cells appeared after seven days post infection （dpi）. Virus titer was different for each strain, TCIDso ranged from 102.7 to 1069, and LDs0 from 1015 to 1075. Five NNV strains named QN 02, QN 05, QN 07, ND 11 and KH 05 had higher virulence than the other three, the first causing 100% mortality in experimental fish 3-5 dpi. NNV KH 05 had the highest antigenic similarity, and it was inactivated completely by 0.2% formalin, 0.002 mol/L binary ethylenimine （BEI） and 0.1% beta-propiolactone. The neutralization antibody titer obtained in fish of groups immunized by BEI 0.002 M and beta-propiolactone 0.1% inactivated virus was four to eight times higher than that of the group treated with the formalin inactivated virus. The antibody titer in fish immunized with beta-propiolactone inactivated virus was more persistent. The efficacy of vaccines developed from beta-propiolactone inactivated virus and aluminium hydroxide （AH） or aluminum phosphate （AP） was observed by intramuscularly immunizing Epinephelusfuscoguttatus size 1.5 cm. Neutralizing antibodies appeared in vaccinated fish on 10th day post-immunization （dpi） at a dilution of 1：16; 1：32 and highest levels were reached on 30-45 dpi, at dilutions of 1：256 and 1：512, after treatment with AH and AP vaccine, respectively. The relative percent of survival （RPS） of vaccine at 30 dpi was highest with challenge doses 0.2-1 × 10^6.8 TCIDs0, the RPS varied from 80%-83.3% in both groups of AH and AP immunization. This result provides the basis for developing a vaccine against NNA disease.展开更多
The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical...The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.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
Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respi...Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population.Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies(NAb) against HAdV-3,-4,-7,-14,-55,and-11 in total 278 healthy populations between 0 months and 49 years of age(228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1–2, 3–5, and 6–17 years,respectively. The seroprevalence was very low(0% - 8.1%) for all other four types. In adults aged between 18 and49 years, HAdV-3,-4, and-7(> 50.00%) were the most common types, followed by HAdV-14(38.00%),-55(34.00%),and-11(24.00%). Adults tended to have high NAb titers against HAdV-4 and-55. HAdV-55-seropositive donors tended to be HAdV-11-and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14,-55,-11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.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
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
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supported by the following grants:the National Key R&D Program of China(Grant 2016YFC1201000 to X.J.)the Institute Fund of Shanghai Public Health Clinical Center(Grant KY-GW-2021-17 to ZH.L.)。
文摘Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.
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.
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.
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This work was supported by the National Natural Science Foundation of China(81672018,81561128008)the National Basic Research Program of China(973program#2014CB542502)+2 种基金the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102)Shanghai Pujiang Program(19PJ1409100)Intramural Funding from Shanghai Public Health Clinical Center.
文摘Raising a heterologous tier 2 neutralizing antibody(nAb)response remains a daunting task for HIV vaccine development.In this study,we explored the utility of diverse HIV-1 envelope(Env)immunogens in a sequential immunization scheme as a solution to this task.This exploration stemmed from the rationale that gp145,a membrane-bound truncation form of HIV Env,may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 form as immunogens in a prime-boost mode.We first showed that gp140 DNA prime-gp145 Tiantan vaccinia(TV)boost likely represents a general format for inducing potent nAb response in mice.However,when examined in rhesus macaque,this modality showed little effectiveness.To improve the efficacy,we extended the original modality by adding a strong protein boost,namely native-like SOSIP.664 trimer displayed on ferritin-based nanoparticle(NP),which was generated by a newly developed click approach.The resulting three-immunization regimen succeeded in eliciting tier-2 nAb response with substantial breadth when implemented in rhesus macaque over a short 8-week schedule.Importantly,the elicited nAb response was able to effectively contain viremia upon a heterologous SHIV challenge.Collectively,our studies highlighted that diversification of Env immunogens,in both types and formulations,under the framework of a sequential immunization scheme might open new opportunity toward HIV vaccine development.
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.
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.
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.
文摘Japanese encephalitis(JE),a vector-borne disease caused by the Japanese encephalitis virus(JEV),remains a major public health concern in South and Southeast Asia[1].JEV,a Flaviviridae family virus,is primarily transmitted by Culex mosquitoes,especially the Culex vishnui subgroup,which breeds extensively in rice fields[1].Birds(Ardeidae family)act as natural reservoirs,while pigs serve as amplifying hosts,and humans are incidental hosts[1].
基金funded by grants from the National Key R&D Program of China(2023YFD1800304)the National Natural Science Foundation of China to QZ(32273041)+1 种基金the Natural Science Foundation of Shaanxi Province of China(2022JC-12)the Central Public interest Scientific Institution Basal Research Fund,National Data Center of Animal Health.
文摘Porcine epidemic diarrhea(PED),caused by porcine epidemic diarrhea virus(PEDV),can induce 80–100%mortality in newborn piglets;therefore,specific and rapid detection methods are important for the prevention of this viral infection.In particular,methods for detecting neutralizing antibodies(nAbs)can be used to evaluate the immunization effect of PEDV vaccines.The spike protein of PEDV(PEDV-S)has been universally used as an antigen to develop immunoassays to detect nAbs.Nanobodies(Nbs)offer advantages such as ease of genetic engineering and low production costs,making them promising for diagnostic applications.In this study,PEDV-S was expressed via the baculovirus system and was used as an antigen to immunize Bactrian camels.A total of 10 Nbs against PEDV-S were first screened and expressed as fusion proteins with horseradish peroxidase(HRP)in HEK293T cells.A Nb-HRP fusion protein named PEDV-S-Nb13-HRP was subsequently selected and used as a probe for developing a competitive enzyme-linked immunosorbent assay(cELISA)to detect anti-PEDV nAbs.Optimization assays identified 80 ng/well of PEDV-S as the optimal coating antigen concentration.The optimal dilution of PEDV-S-Nb13-HRP was 1:200,and the optimal serum dilution was 1:10.The cutoff value of cELISA was determined as 28.1%,demonstrating high specificity,repeatability,stability,and good agreement rates with two commercial ELISA kits(93.6%)and a serum neutralization test(96.34%).Additionally,the results of the detection of IgA antibodies in oral and milk samples from sows were in good agreement with those of the IDEXX PEDV IgA kit.These results demonstrate that the cELISA is a reliable and cost-effective method for detecting anti-PEDV nAbs.
文摘In-utero exposure to Zika virus(ZIKV)could lead to miscarriage,preterm birth and congenital Zika syndrome.This study aimed at estimating the burden of ZIKV and Dengue virus(DENV)infections among pregnant women in Bojude,Nigeria.A total of 200 blood samples were collected from pregnant women between February and April 2022.Using the updated CDC guidelines for the diagnosis of ZIKV infections,including ELISA and microneutralization test(MNT),we found that 16.5%of participants were positive for ZIKV IgM,10%were positive for IgG,and 23%had nAb in their serum.Among the 46 ZIKV nAb-positive women,52.2%and 10.9%were recent and previous ZIKV infections,respectively,while 6.5%had previous DENV infections.Although no recent DENV infection was detected,recent and previous ZIKV/DENV co-infections were 13.0%and 17.4%,respectively.Two participants had recent secondary ZIKV infections,while 39.1%had prolonged lifelong immunity.Recent ZIKV infection rates were significantly higher among sexually active females aged 20–29 years than other age groups,with the highest risk observed in the first trimester of pregnancy.In addition,the grand-multiparous women are at higher risk of ZIKV infections than other categories.Monotypic recent,secondary and past ZIKV infections,as well as DENV and ZIKV co-infections,were detected in both the asymptomatic and symptomatic pregnant women.These findings highlight that ZIKV infection is prevalent among pregnant women in Nigeria and underscore the associated risk factors,providing evidence-based information on the burden of ZIKV infections in DENV-endemic region.
基金support by National Natural Science Foundation of China under Grant(81800095)Key Scientific and Technological Project of Hubei province(2020FCA004)。
文摘COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients.Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected.The median age of the studied cohort was59.83±12.94 years.All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to112 days PIS.Peripheral lymphocytes counts were normal.The ratios of interferon gamma(IFN-c)-secreting cells to total CD4^(+)and CD8^(+)cells were normal as 24.68%±9.60%and 66.41%±14.87%respectively.However,the number of IFNc-secreting NK cells diminished(58.03%±11.78%).All patients presented detectable IgG,which positively correlated with mild neutralizing activity(Mean value neutralisation antibodies titers=157.2,P=0.05).No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS,and the cytopathic effect was lacking.But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages.Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions.In conclusion,decreased IFN-c production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence.Further,low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARSCoV-2 infection.
文摘Eight strains of nervous necrosis virus （NNV） isolated in Vietnam were used to detect the pathogenicity and immune response in sea bass （SB）. All strains induced cytopathic effect in SB cell line, complete destruction of monolayer of cells appeared after seven days post infection （dpi）. Virus titer was different for each strain, TCIDso ranged from 102.7 to 1069, and LDs0 from 1015 to 1075. Five NNV strains named QN 02, QN 05, QN 07, ND 11 and KH 05 had higher virulence than the other three, the first causing 100% mortality in experimental fish 3-5 dpi. NNV KH 05 had the highest antigenic similarity, and it was inactivated completely by 0.2% formalin, 0.002 mol/L binary ethylenimine （BEI） and 0.1% beta-propiolactone. The neutralization antibody titer obtained in fish of groups immunized by BEI 0.002 M and beta-propiolactone 0.1% inactivated virus was four to eight times higher than that of the group treated with the formalin inactivated virus. The antibody titer in fish immunized with beta-propiolactone inactivated virus was more persistent. The efficacy of vaccines developed from beta-propiolactone inactivated virus and aluminium hydroxide （AH） or aluminum phosphate （AP） was observed by intramuscularly immunizing Epinephelusfuscoguttatus size 1.5 cm. Neutralizing antibodies appeared in vaccinated fish on 10th day post-immunization （dpi） at a dilution of 1：16; 1：32 and highest levels were reached on 30-45 dpi, at dilutions of 1：256 and 1：512, after treatment with AH and AP vaccine, respectively. The relative percent of survival （RPS） of vaccine at 30 dpi was highest with challenge doses 0.2-1 × 10^6.8 TCIDs0, the RPS varied from 80%-83.3% in both groups of AH and AP immunization. This result provides the basis for developing a vaccine against NNA disease.
文摘The Z 10 and Z 37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil ( Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.
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supported by the National Key Research and Development Program of China (2018YFC1200100)the Guangzhou Science and Technology Program Key Project, China (201803040004)+2 种基金the National Science and Technology Major Project of China (2017ZX10103011003, 2018ZX10102001)the National Natural Science Foundation of China, China (31570163)the Youth Project of State Key Laboratory of Respiratory Disease, China (SKLRD-QN-201713)。
文摘Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population.Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies(NAb) against HAdV-3,-4,-7,-14,-55,and-11 in total 278 healthy populations between 0 months and 49 years of age(228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1–2, 3–5, and 6–17 years,respectively. The seroprevalence was very low(0% - 8.1%) for all other four types. In adults aged between 18 and49 years, HAdV-3,-4, and-7(> 50.00%) were the most common types, followed by HAdV-14(38.00%),-55(34.00%),and-11(24.00%). Adults tended to have high NAb titers against HAdV-4 and-55. HAdV-55-seropositive donors tended to be HAdV-11-and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14,-55,-11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.
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.·
