Temporal Profiles of Antibody Responses, Cytokines, and Survival of COVID-19 Patients: A Retrospective Cohort

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.

Original Antigenic Sin on Antibody Response in SARS-CoV-2 Infection

Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infections. Owing to the original antigenic sin (OAS), variant breakthrough infection or vaccination potentially induces a stronger antibody response against the ancestral strain than to subsequent variants, as in the case of influenza. Thus, overcoming OAS is important for the development of future vaccine designs. This review summarizes the recent findings on OAS in the antibody response to SARS-CoV-2 and its variants, with an emphasis on future vaccine designs.

DYNAMICS ANALYSIS OF A DELAYED HIV INFECTION MODEL WITH CTL IMMUNE RESPONSE AND ANTIBODY IMMUNE RESPONSE

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.

Clinical application of COVID-19 vaccine in liver transplant recipients

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

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.

Human IgM and IgG Responses to an Inactivated SARS-CoV-2 Vaccine

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.

Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

AIM： In the present study, antibody and peripheral blood mononuclear cells （PBMC） proliferative responses against hepatitis C virus （HCV） antigens were evaluated in HCV chronically infected patients. METHODS： Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay （ELISA） and carboxyfluorescein succinimidyl ester staining. RSULTS： Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM （P = 0.027） and IgG （P = 0.0006） was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid （P = 0.017） and NS3 （P = 0.005） after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage （P = 0.036）. IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4＋ or CD8＋ T cells, being the capsid poorly recognized. CONCLUSION： These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.

Antigen Gene Cloning and Expression of HIV-1 for AIDS Vaccine Design Ⅲ. HIV-1 Antigen Gene Cloning, in Vitro Expression and Antibody Induction

Objective: To evaluate the humoral immune induction in rats of a candidate AIDS vaccine expressing the gag p24 gene froma subtype B HIV-1 isolate. Methods: The amplified p24 gene was inserted into aneukaryotic expression vector to form the supercoiled DNAvaccine. The linearized expressed DNA vaccine was preparedfrom the expression plasmid by polymerase chain reaction(PCR). The antigen gene expression in rats of the linearizedand supercoiled DNA vaccines were in vitro and in vivodetected. Results: In vitro transcription and Northern hybridizationshowed that the linearized DNA vaccine could synthesizeamounts or p24 mRNA similar to the supercoiled DNA vaccine.Antibody assays of inoculated rats confirmed that thelinearized expression DNA could induce a slightly higherantibody titer than the expression plasmid, while the highestautibody titer had been induced by plasmid plus adjuvantinoculation. Conclusion: The construction of a candidate AIDS vaccinebased on the p24 gene could shed light on a potential IV vaccine, meriting evaluation in a rhesus macaque SHIV-AIDSmodel.

结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性

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.

H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease

AIM: To determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) anti- body response to these proteins in increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of anti- heat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence of H pylori infec- tion was 78.7% (n = 63) in patients and 76.2% (n = 122) in controls (P = 0.07). Patients infected by CagA- positive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Sys-temic levels of IgG to Hsp60 were increased in H pylori- negative patients compared with uninfected controls (P < 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of anti- Hsp60 antibodies may constitute a marker and/or a con- comitant pathogenic factor of the disease.

Immunogenicity of recombinant hepatitis B virus vaccine in patients with and without chronic hepatitis C virus infection:A case-control study

AIM： To compare the response of standard hepatitis B virus （HBV） vaccination between patients with chronic hepatitis C virus （HCV） infection and healthy individuals. METHODS： This is a prospective case-control study. A total of 38 patients with chronic HCV infection and 40 healthy controls were included. Vaccination was performed by injection of 20μg recombinant HBsAg into the deltoid muscle at mo 0,1 and 6. Anti-HBs concentration was determined 3 mo after the last dose and compared between the two groups. The response pattern was characterized as （1） high-response when the anti-HBs antibody titer was 〉 100 IU/L, （2） low-response when the titer was 10-100 IU/L. and （3） no-response when the titer was 〈 10 IU/L. RESULTS： In the patient group, there were 10/38 （26.3%） non-responders, 8/38 （21.1%） Iow-responders and 20/38 （52.6%） high-responders. The corresponding values in the control group were 2/40 （5.0%）, 7/40 （17.5%） and 31/40 （77.5%）, respectively. The response pattern was statistically different between the two groups. In multivariate analysis, smoking was a significant confounder, while HCV infection lost its significant correlation with lower antibody response. CONCLUSION： Patients with chronic HCV infection tend to respond weakly to HBV vaccination compared to healthy individuals, though this correlation is not independent according to multivariate analysis.

Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases

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.

Viral and Antibody Kinetics of COVID-19 Patients with Different Disease Severities in Acute and Convalescent Phases:A 6-Month Follow-Up Study

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.

Effect of experimental single Ancylostoma caninum and mixed infections of Trypanosoma brucei and Trypanosoma congolense on the humoural immune response to anti-rabies vaccination in dogs

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.

Replication priority of hepatitis C virus genotype 2a in a Chinese cohort

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.

Long-term asymptomatic SARS-CoV-2 infection associated with deficiency on multiple immune cells

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.

Highly Prevalent SARS-CoV-2 Antigenemia in COVID-19 Patients

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.

Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases

Background and Aims:SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports.However,the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases(AILD)is still unknown.Methods:Eighty-four patients with AILD were prospectively followed up after the second dose(primary)of inactivated SARS-CoV-2 vaccine.Some of them received the third dose(booster)of inactivated vaccine.Adverse events(AEs),autoimmune activation,and liver inflammation exacerbation after primary and booster vaccination were recorded.Meanwhile,dynamics of antireceptor-binding-domain IgG(anti-RBD-IgG),neutralizing antibodies(NAbs)and RBD-specific B cells responses were evaluated.Results:The overall AEs in AILD patients after primary and booster vaccination were 26.2%and 13.3%,respectively.The decrease of C3 level and increase of immunoglobulin light chain K andλlevels were observed in AILD patients after primary vaccination,however,liver inflammation was not exacerbated,even after booster vaccination.Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination.Notably,the antibody titers were significantly elevated after booster vaccination(10-fold in anti-RBD-IgG and 7.4-fold in NAbs,respectively),which was as high as in healthy controls.Unfortunately,the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants.Changes of atypical memory B cells were inversely related to antibody levels,which indicate that the impaired immune memory was partially restored partly by the booster vaccination.Conclusions:The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.