The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the tempora...The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the temporal profiles of specific antibodies,as well as the associations between the antibodies,proinflammatory cytokines,and survival of patients with coronavirus disease 2019(COVID-19).A total of 1830 laboratory-confirmed COVID-19 cases were recruited.The temporal profiles of the virus,antibodies,and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method.The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis.Of the 1830 patients,1435 were detectable for SARS-CoV-2,while 395 were positive in specific antibodies only.Of the 1435 patients,2.4%presented seroconversion for neither immunoglobulin G(IgG)nor immunoglobulin M(IgM)during hospitalization.The seropositive rates of IgG and IgM were 29.6%and 48.1%,respectively,in the first week,and plateaued within five weeks.For the patients discharged from the hospital,the IgM decreased slowly,while high levels of IgG were maintained at around 188 AUmL^(-1) for the 12 weeks since illness onset.In contrast,in the patients who subsequently died,IgM declined rapidly and IgG dropped to 87 AUmL^(-1) at the twelfth week.Elevated interleukin-6,interleukin-8,interleukin-10,interleukin-1b,interleukin-2R,and tumor necrosis factor-a levels were observed in the deceased patients in comparison with the discharged patients,and 12.5%of the association between IgG level and mortality risk was mediated by these cytokines.Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival,which may help to guide prognosis estimation.展开更多
In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free viru...In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.展开更多
Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate ...Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.展开更多
Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in ...Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.Methods:All subjects aged 18-60 years who did not have SARS-CoV-2 infection at the time of screening from June 19,2021,to July 02,2021,were approached for inclusion.All participants received two doses of inactivated SARS-CoV-2 vaccine.Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination.A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL.This retrospective study included 97 infection-naive individuals(mean age 35.6 years;37.1%male,62.9%female).Results:The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1%and 74.2%,respectively.IgG antibody levels were significantly higher than IgM levels(P<0.0001).Sex had no effect on IgM and IgG antibody response after the second dose.The mean anti-IgG level in older persons(≥42 years)was significantly lower than that of younger recipients.There was a significantly lower antibody level at>42 days compared to that at 0-20 days(P<0.05)and 21-31 days(P<0.05)after the second dose.Conclusion:IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals(>18 years),which can be influenced by age and detection time after the second dose of vaccination.展开更多
Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-asso...Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures.To overcome these obstacles,we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous,stromal,and healthy mucosa cells.N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatographyelectrospray ionization tandem mass spectrometry,enabling the differentiation and structural characterization of isomeric species.In total,116 N-glycans were identified that showed profound differences in expression among cancer,stroma,and normal mucosa.In comparison with healthy mucosa,the cancer cells showed an increase in a2-6 sialylation and monoantennary N-glycans,as well as a decrease in bisected N-glycans.Moreover,specific sialylated and(sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers.In comparison with cancer,the stroma showed lower levels of oligomannosidic and monoantennary N-glycans,LewisA/X epitopes,and sulfation,as well as increased expression of(core-)fucosylation and a2-3 sialylation.Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues,proving the necessity of their separate analysis for the discovery of cancer-associated glycans.展开更多
Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Th...Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.展开更多
Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly around the world,posing a major threat to human health and the economy.Currently,long-term da...Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly around the world,posing a major threat to human health and the economy.Currently,long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited.Herein,we report the clinical features,viral RNA loads,and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People’s Hospital,Hubei Province,China.Overall,5.36%(6/112)of patients showed persistent viral RNA shedding(>45 days).The peak viral load was higher in the severe disease group than in the mild group(median cycle threshold value,36.4 versus 31.5;P=0.002).For most patients the disappearance of IgM antibodies occurred approximately 4–6 weeks after symptoms onset,while IgG persisted for over 194 days after the onset of symptoms,although patients showed a 46%reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase.We also studied18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients,and the asymptomatic individuals were the close contacts of these symptomatic cases.Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals.These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection,and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.展开更多
Objective:To determine the effect of Ancylostoma caninum(A.caninum)and trypanosome parasites on the immune response to vaccination in dogs in endemic environments.Methods:Sixteen dogs for the experiment were grouped i...Objective:To determine the effect of Ancylostoma caninum(A.caninum)and trypanosome parasites on the immune response to vaccination in dogs in endemic environments.Methods:Sixteen dogs for the experiment were grouped into 4 of 4 members each.Group I was the uninfected control one,and GPII was infected with A.caninum;GPIII was infected with A.caninum/Trypanosoma congolense(T.congolense),and GPIV was infected with Trypanosoma brucei(T.brucei)/A.caninum.The dogs were first vaccinated with antirabies vaccine before infecting GPII,GPIII and GPIV with A.caninum which were done 4 weeks after vaccination.By 2-week post-vaccination,trypanosome parasites were superimposed on both GPIII and GPIV.A secondary vaccination was given to GPI,GPII,GPIII,and GPIV by Week 12 of the experiment(4 weeks post treatment).Results:The prepatent period was(3.00±1.40)days,in the conjunct infection of T.brucei/A.caninum.It was(9.00±1.10)days,in conjunct T.congolense/A.caninum.The prepatent period of A.caninum was(14.0±2.0)days in the single A.caninum group and(13.0±1.0)days in the conjunct trypanosome/A.caninum.At the 1st week after vaccination,the antibody titer in all the vaccinated groups(GPI,GPII,GPIII,and GPIV)significantly increased(P<0.05)and peaked at the 3rd week after vaccination.Following infections,there were marked significant decreases(P<0.05)in the antibody production against rabies in GPII,GPIII and GPIV.The significant decrease(P<0.05)in antibody titer was highest in the conjunct groups(GPIII and GPIV)compared to the single infection(GPII).Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs.A secondary vaccination administered at the 12th week after the primary vaccination significantly increased(P<0.05)the antibody titer with a peak at the 3rd week after the secondary vaccination.Conclusions:It was therefore concluded that A.caninum,T.brucei and T.congolense induced immunosuppression in antirabies vaccination in dogs.展开更多
HCV genotypes have been documented in clinical practice.The aim of this study was to determine the replication priority of different HCV genotypes in a Chinese HCV positive cohort.Serum samples from 491 apparently hea...HCV genotypes have been documented in clinical practice.The aim of this study was to determine the replication priority of different HCV genotypes in a Chinese HCV positive cohort.Serum samples from 491 apparently healthy Chinese blood donors testing positive for HCV antibodies and naive to antiviral drug therapy were tested.Genotyping analysis showed that genotypes 1b and 2a were predominant and accounted for 77.6%of the HCV infections.Among the genotype groups,individuals infected with genotype 2a had an HCV RNA viral load(108 copies/mL)about 200-fold(lg,2.3)greater than those infected with other genotypes(10^(4)–10^(5)copies/mL)indicating a replication priority of genotype 2a.However,there was no correlation between HCV genotype and antibody response suggesting that the amplification advantage of genotype 2a results from a favorable interaction with the host cellular environment.In conclusion,HCV genotypes 1b and 2a are the predominant genotypes in China and genotype 2a possesses a significant replication priority compared with the other genotypes.This suggests the existence of host cellular factors that may act as drug-targets for entirely clearing HCV infection in the future.展开更多
The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)infection cases,especially in immuno‐compromised individuals,remain largely unknow...The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)infection cases,especially in immuno‐compromised individuals,remain largely unknown.Here we present a case of asymptomatic SARS‐CoV‐2 infection that lasted for at least 67 days.The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70,plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57.Throughout the infection,no anti‐SARS‐CoV‐2 specific IgM or IgG antibodies were detected.Instead,the patient showed either a low percentage or an absolute number of non‐classical monocytes,dendritic cells(DCs),CD4^(+)T cells,and regulatory T cells(Tregs),which may account for the clinical feature and absence of antibody response.This case may shed new light on the outbreak management related to control/prevention,treatment,and vaccination of SARS‐CoV‐2 and other virus infections in immunocompromised individuals.展开更多
Background:Many issues,such as severity assessment and antibody responses,remain to be answered eagerly for evaluation and understanding of COVID-19.Immune lesion is one of key pathogenesis of the disease.It would be ...Background:Many issues,such as severity assessment and antibody responses,remain to be answered eagerly for evaluation and understanding of COVID-19.Immune lesion is one of key pathogenesis of the disease.It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection.Methods:A total of 156 patients admitted to the First People’s Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study.SARS-CoV-2 nucleocapsid(NP)antigen,specific IgM/IgG antibodies,and RNA were detected in sequential sera from three COVID-19 patients,and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay,colloidal gold quick diagnosis,and real-time RT-PCR,respectively.The clinical types of COVID-19 patients were classified into asymptomatic,mild,moderate,severe,and critical,following on the Chinese guideline of COVID-19 diagnosis and treatment.The demographic and clinical data of patients were obtained for comparable analysis.Results:NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms,and 60.13%(92/153)expanded samples collected within 17days after illness onset.No SARS-CoV-2 RNA segment was detected in these sera.The NP positive proportion reached a peak(84.85%,28/33)on 6 to 8days after illness onset.Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19.Compared to NP negativepatients,NP positive patients had older age[years,medians(interquartileranges(IQR)),49(6)vs.31(11)],lowerpositive proportion of NP specific IgM[27.17%(25/92)vs.59.02%(36/61)],and IgG[21.74%(20/92)vs.59.02%(36/61)]antibodies,and longer duration[days,medians(IQR),24(10)vs.21(13)]from illness to recovery.Conclusions:SARS-CoV-2 NP antigenemia occurred in COVID-19,and presented highly prevalent at early stage of the disease.The antigenemia was related to clinical severity of the disease,and may beresponsible for the delay of detectable SARS-Cov-2IgM.展开更多
基金supported by the National Natural Science Foundation of China(81572017)the National Key Research and Development Plan Program of China(2016YFC1302702 and 2020YFC0860800)+1 种基金the Revitalization Projects after the COVID-19 Plague of the China Association for Science and Technology(20200608CG111311)the Emergency Research Projects for COVID-19 Prevention and Control of the Wuhan Health Commission(EG20M01)。
文摘The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known.Thus,we sought to analyze the temporal profiles of specific antibodies,as well as the associations between the antibodies,proinflammatory cytokines,and survival of patients with coronavirus disease 2019(COVID-19).A total of 1830 laboratory-confirmed COVID-19 cases were recruited.The temporal profiles of the virus,antibodies,and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method.The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis.Of the 1830 patients,1435 were detectable for SARS-CoV-2,while 395 were positive in specific antibodies only.Of the 1435 patients,2.4%presented seroconversion for neither immunoglobulin G(IgG)nor immunoglobulin M(IgM)during hospitalization.The seropositive rates of IgG and IgM were 29.6%and 48.1%,respectively,in the first week,and plateaued within five weeks.For the patients discharged from the hospital,the IgM decreased slowly,while high levels of IgG were maintained at around 188 AUmL^(-1) for the 12 weeks since illness onset.In contrast,in the patients who subsequently died,IgM declined rapidly and IgG dropped to 87 AUmL^(-1) at the twelfth week.Elevated interleukin-6,interleukin-8,interleukin-10,interleukin-1b,interleukin-2R,and tumor necrosis factor-a levels were observed in the deceased patients in comparison with the discharged patients,and 12.5%of the association between IgG level and mortality risk was mediated by these cytokines.Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival,which may help to guide prognosis estimation.
基金The work was supported by NSF of China(11201002)Natural Science Foundation of Universities in Anhui Province(KJ2017A815).
文摘In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.
基金Supported by The Tonjes-Vagt-Stiftung,Bremen,Germany.
文摘Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.
基金supported by grants from the Applied Basic Research Key Project of Wuhan Municipal Bureau of Science and Technology(No.2020020601012218)the Fundamental Research Funds for the Central Universities(HUST COVID-19 Rapid Response Call No.2020kfyXGYJ040)National Natural Science Foundation of China(No.81802090).
文摘Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.Methods:All subjects aged 18-60 years who did not have SARS-CoV-2 infection at the time of screening from June 19,2021,to July 02,2021,were approached for inclusion.All participants received two doses of inactivated SARS-CoV-2 vaccine.Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination.A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL.This retrospective study included 97 infection-naive individuals(mean age 35.6 years;37.1%male,62.9%female).Results:The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1%and 74.2%,respectively.IgG antibody levels were significantly higher than IgM levels(P<0.0001).Sex had no effect on IgM and IgG antibody response after the second dose.The mean anti-IgG level in older persons(≥42 years)was significantly lower than that of younger recipients.There was a significantly lower antibody level at>42 days compared to that at 0-20 days(P<0.05)and 21-31 days(P<0.05)after the second dose.Conclusion:IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals(>18 years),which can be influenced by age and detection time after the second dose of vaccination.
文摘Aberrant glycosylation is considered to be a hallmark of colorectal cancer(CRC),as demonstrated by various studies.While the N-glycosylation of cell lines and serum has been widely examined,the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures.To overcome these obstacles,we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous,stromal,and healthy mucosa cells.N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatographyelectrospray ionization tandem mass spectrometry,enabling the differentiation and structural characterization of isomeric species.In total,116 N-glycans were identified that showed profound differences in expression among cancer,stroma,and normal mucosa.In comparison with healthy mucosa,the cancer cells showed an increase in a2-6 sialylation and monoantennary N-glycans,as well as a decrease in bisected N-glycans.Moreover,specific sialylated and(sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers.In comparison with cancer,the stroma showed lower levels of oligomannosidic and monoantennary N-glycans,LewisA/X epitopes,and sulfation,as well as increased expression of(core-)fucosylation and a2-3 sialylation.Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues,proving the necessity of their separate analysis for the discovery of cancer-associated glycans.
基金This work was supported by the Beijing Natural Science Foundation(M23008)the National Key Research and Development Program of China(2018YFE0207300)+2 种基金Beijing Municipal Science&Technology Commission(Z211100002521021)the National High Level Hospital Clinical Research Funding(2022-PUMCH-B-124)Key Research and Development Plan of Hebei Province,Special Health Innovation Project(22377744D).
文摘Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
基金supported by grants from the National Science and Technology Major Project of China(2018ZX10301202-003)the Collaboration and Innovation Health Care Major Project of Guangzhou(201803040013)。
文摘Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread rapidly around the world,posing a major threat to human health and the economy.Currently,long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited.Herein,we report the clinical features,viral RNA loads,and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People’s Hospital,Hubei Province,China.Overall,5.36%(6/112)of patients showed persistent viral RNA shedding(>45 days).The peak viral load was higher in the severe disease group than in the mild group(median cycle threshold value,36.4 versus 31.5;P=0.002).For most patients the disappearance of IgM antibodies occurred approximately 4–6 weeks after symptoms onset,while IgG persisted for over 194 days after the onset of symptoms,although patients showed a 46%reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase.We also studied18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients,and the asymptomatic individuals were the close contacts of these symptomatic cases.Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals.These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection,and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.
基金Supported by the Tertiary Education Trust Fund(TETFUND)(Grant No.MOUAU/ETF/DO/40/VOL.1/59).
文摘Objective:To determine the effect of Ancylostoma caninum(A.caninum)and trypanosome parasites on the immune response to vaccination in dogs in endemic environments.Methods:Sixteen dogs for the experiment were grouped into 4 of 4 members each.Group I was the uninfected control one,and GPII was infected with A.caninum;GPIII was infected with A.caninum/Trypanosoma congolense(T.congolense),and GPIV was infected with Trypanosoma brucei(T.brucei)/A.caninum.The dogs were first vaccinated with antirabies vaccine before infecting GPII,GPIII and GPIV with A.caninum which were done 4 weeks after vaccination.By 2-week post-vaccination,trypanosome parasites were superimposed on both GPIII and GPIV.A secondary vaccination was given to GPI,GPII,GPIII,and GPIV by Week 12 of the experiment(4 weeks post treatment).Results:The prepatent period was(3.00±1.40)days,in the conjunct infection of T.brucei/A.caninum.It was(9.00±1.10)days,in conjunct T.congolense/A.caninum.The prepatent period of A.caninum was(14.0±2.0)days in the single A.caninum group and(13.0±1.0)days in the conjunct trypanosome/A.caninum.At the 1st week after vaccination,the antibody titer in all the vaccinated groups(GPI,GPII,GPIII,and GPIV)significantly increased(P<0.05)and peaked at the 3rd week after vaccination.Following infections,there were marked significant decreases(P<0.05)in the antibody production against rabies in GPII,GPIII and GPIV.The significant decrease(P<0.05)in antibody titer was highest in the conjunct groups(GPIII and GPIV)compared to the single infection(GPII).Treatment with diminazene aceturate and mebendazole did not significantly improve antibody response in the dogs.A secondary vaccination administered at the 12th week after the primary vaccination significantly increased(P<0.05)the antibody titer with a peak at the 3rd week after the secondary vaccination.Conclusions:It was therefore concluded that A.caninum,T.brucei and T.congolense induced immunosuppression in antirabies vaccination in dogs.
基金This study was supported by the“Key Program for the Control of Infectious Diseases”(Grant No.2005DIB1J090)the 973 Program of the Ministry of Science and Technology of the People's Republic of China(Grant No.2004CB518901,Jian-Dong Jiang).
文摘HCV genotypes have been documented in clinical practice.The aim of this study was to determine the replication priority of different HCV genotypes in a Chinese HCV positive cohort.Serum samples from 491 apparently healthy Chinese blood donors testing positive for HCV antibodies and naive to antiviral drug therapy were tested.Genotyping analysis showed that genotypes 1b and 2a were predominant and accounted for 77.6%of the HCV infections.Among the genotype groups,individuals infected with genotype 2a had an HCV RNA viral load(108 copies/mL)about 200-fold(lg,2.3)greater than those infected with other genotypes(10^(4)–10^(5)copies/mL)indicating a replication priority of genotype 2a.However,there was no correlation between HCV genotype and antibody response suggesting that the amplification advantage of genotype 2a results from a favorable interaction with the host cellular environment.In conclusion,HCV genotypes 1b and 2a are the predominant genotypes in China and genotype 2a possesses a significant replication priority compared with the other genotypes.This suggests the existence of host cellular factors that may act as drug-targets for entirely clearing HCV infection in the future.
基金funded by Natural Science Foundation of Hebei Province granted to XC(no.H2020206352)Novel Coronavirus Project to GH by Jiangmen Science and Technology Bureau(2020020500410003915)Guangzhou Emergency Response Plan to D.L(EKPG21-27)。
文摘The immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)infection cases,especially in immuno‐compromised individuals,remain largely unknown.Here we present a case of asymptomatic SARS‐CoV‐2 infection that lasted for at least 67 days.The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70,plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57.Throughout the infection,no anti‐SARS‐CoV‐2 specific IgM or IgG antibodies were detected.Instead,the patient showed either a low percentage or an absolute number of non‐classical monocytes,dendritic cells(DCs),CD4^(+)T cells,and regulatory T cells(Tregs),which may account for the clinical feature and absence of antibody response.This case may shed new light on the outbreak management related to control/prevention,treatment,and vaccination of SARS‐CoV‐2 and other virus infections in immunocompromised individuals.
基金This study was supported by National Mega-projects for Infectious Diseases(2017ZX10304402-001-019)National Natural Scientific Foundation of China(81971946)Hefei Municipal Health Commission(hwk2018zd001).
文摘Background:Many issues,such as severity assessment and antibody responses,remain to be answered eagerly for evaluation and understanding of COVID-19.Immune lesion is one of key pathogenesis of the disease.It would be helpful to understand the disease if an investigation on antigenemia and association was conducted in the patients with SARS-CoV-2 infection.Methods:A total of 156 patients admitted to the First People’s Hospital of Hefei or Anhui Provincial Hospital on January to February 2020 were involved in this study.SARS-CoV-2 nucleocapsid(NP)antigen,specific IgM/IgG antibodies,and RNA were detected in sequential sera from three COVID-19 patients,and additional 153 COVID-19 patients by means of NP-antigen capture enzyme-linked immunosorbent assay,colloidal gold quick diagnosis,and real-time RT-PCR,respectively.The clinical types of COVID-19 patients were classified into asymptomatic,mild,moderate,severe,and critical,following on the Chinese guideline of COVID-19 diagnosis and treatment.The demographic and clinical data of patients were obtained for comparable analysis.Results:NP antigen was detected in 5 of 20 sequential sera collected from three COVID-19 patients with typically clinical symptoms,and 60.13%(92/153)expanded samples collected within 17days after illness onset.No SARS-CoV-2 RNA segment was detected in these sera.The NP positive proportion reached a peak(84.85%,28/33)on 6 to 8days after illness onset.Both NP concentration and positive proportion were increased with the increase of clinical severity of COVID-19.Compared to NP negativepatients,NP positive patients had older age[years,medians(interquartileranges(IQR)),49(6)vs.31(11)],lowerpositive proportion of NP specific IgM[27.17%(25/92)vs.59.02%(36/61)],and IgG[21.74%(20/92)vs.59.02%(36/61)]antibodies,and longer duration[days,medians(IQR),24(10)vs.21(13)]from illness to recovery.Conclusions:SARS-CoV-2 NP antigenemia occurred in COVID-19,and presented highly prevalent at early stage of the disease.The antigenemia was related to clinical severity of the disease,and may beresponsible for the delay of detectable SARS-Cov-2IgM.
