自新冠疫情暴发以来,新冠病毒不断进化,Omicron作为第五个世界卫生组织公布的值得关注的变异株(variants of concern,VOCs),在基因组学、生物学以及流行病学特征上与之前的VOCs存在明显差异。虽然Omicron感染导致的重症率和死亡率相对其...自新冠疫情暴发以来,新冠病毒不断进化,Omicron作为第五个世界卫生组织公布的值得关注的变异株(variants of concern,VOCs),在基因组学、生物学以及流行病学特征上与之前的VOCs存在明显差异。虽然Omicron感染导致的重症率和死亡率相对其他VOCs明显下降,但其极强的传播力不断突破既往感染和疫苗建立的人群免疫屏障和防疫壁垒,可以说Omicron揭开了新冠疫情防控的新篇章。本文对Omicron变异株及其亚种的基因组学、生物学、流行病学特征及其与流感病毒的差异进行阐述,以期为优化疫情防控策略提供科学依据。展开更多
目的观察甲型肝炎(甲肝)减毒活疫苗(Hepatitis A Attenuated Live Vaccine,HepA-L)不同免疫程序免疫后7年的抗体持久性,并与甲肝灭活疫苗(Hepatitis A Inactivated Vaccine,HepA-I)进行比较。方法按个体随机的方法,把筛检出的甲肝易感...目的观察甲型肝炎(甲肝)减毒活疫苗(Hepatitis A Attenuated Live Vaccine,HepA-L)不同免疫程序免疫后7年的抗体持久性,并与甲肝灭活疫苗(Hepatitis A Inactivated Vaccine,HepA-I)进行比较。方法按个体随机的方法,把筛检出的甲肝易感者随机分为A、B、C三组。A组按0、6、12个月程序接种3剂国产H2株HepA-L,B、C两组按0、6个月程序分别接种HepA-L和HepA-I,分别于免疫后1、6、7、12、13、24、84个月采集血清标本,检测抗甲肝病毒抗体(Anti-hepatitis A Virus Antibody,Anti-HAV)总抗体。结果三组Anti-HAV阳性率均于接种第2剂后1个月达100%,抗体峰值几何平均浓度(Geometric Mean Concentration,GMC)以C组最高,为2938.1mIU/ml(毫国际单位/毫升),A、B组分别为1315.6mIU/ml、1586.0mIU/ml。A组于12个月时再加强免疫1剂,抗体GMC上升,达1945.3mIU/ml。首剂免疫后84个月,Anti-HAV阳性率三组均保持100%,尽管A组抗体GMC降至336.8mIU/ml,仍显著高于B、C两组。结论HepA-L近期加强免疫效果良好,抗体反应与持久性同HepA-I相当,远期效果有待于进一步观察。展开更多
目的了解新生儿重组乙型肝炎(乙肝)疫苗(酿酒酵母)[Hepatitis B Vaccine(HepB)Made by Recombinant Deoxyribonucleic Acid(DNA)Techniques in Saccharom yces cerevisiae Yeast,HepB-SCY]初次免疫(初免)的血清学效果,以及低/无应答状...目的了解新生儿重组乙型肝炎(乙肝)疫苗(酿酒酵母)[Hepatitis B Vaccine(HepB)Made by Recombinant Deoxyribonucleic Acid(DNA)Techniques in Saccharom yces cerevisiae Yeast,HepB-SCY]初次免疫(初免)的血清学效果,以及低/无应答状况和影响因素,探索不同再免疫方案的血清学效果。方法对1212名按照0、1、6个月免疫程序完成5微克(μg)HepB-SCY3剂免疫≥1个月的7～12月龄儿童,采血分离血清,用化学发光微粒子免疫分析法(Chemilum inescence Microparticle Immunoassay,CMIA)定量检测抗乙肝病毒表面抗原抗体[Antibody to Hepatitis B Virus(HBV)Surface Antigen,Anti-HBs(HBsAg)]。对低/无应答者随机分为2组,分别用5μg HepB-SCY或10μg HepB(汉逊酵母)(HepB Mabe By Becombinant DNA Fediniguesin Hansenula palym orpha Yeast,HepB-HPY)再免疫3剂,并分别检测再免疫1剂和3剂后的Anti-HBs。结果 HepB-SCY3剂初免后,Anti-HBs阳性[≥10毫国际单位/毫升(mIU/ml)]率、正常应答(Anti-HBs≥100m IU/ml)率、低应答(HBsAg阴性,10m IU/ml≤Anti-HBs<100m IU/ml)率、无应答(Anti-HBs<10m IU/ml,且HBV DNA和HBsAg均阴性)率和HBsAg阳性率,分别为98.43%、87.05%、11.39%、0.99%和0.58%。多因素Logistic回归分析显示,母亲HBsAg阳性的新生儿初免后的Anti-HBs应答率,低于母亲HBsAg阴性的新生儿[比值比(Odds Ratio,OR)=2.409,P=0.015]。低/无应答者使用HepB-SCY或HepB-HPY再免疫1剂(145例)及3剂(136例)后,Anti-HBs阳转率从再免疫前的91.72%分别上升到97.93%和99.26%,正常应答率分别达到82.76%和96.32%,Anti-HBs几何平均浓度(Geometry Mean Concentration,GMC)比再免疫前上升7.86倍和19.7倍。其中5μg HepB-SCY组再免疫3剂后的Anti-HBs应答率,明显高于再免疫1剂者(Χ2=12.54,P<0.001);10μg HepB-HPY组再免疫3剂者,与再免疫1剂的应答率差异无统计学意义(Χ2=2.58,P=0.108)。两种疫苗再免疫1剂比再免疫前(HepB-HPY组u=10.32,P<0.001;HepB-SCY组u=-8.53,P<0.001)、再免疫3剂比再免疫1剂(HepB-HPY组u=-3.59,P<0.001展开更多
Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and ...Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor activity.However,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated vaccines.Methods:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this study.The amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third dose.Results:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in PLWH.Interestingly,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay.Compared with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs.Additionally,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T cells.However,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was insignificant at 4W and 12W,except at 0W.Conclusi展开更多
目的评价中国仓鼠卵巢细胞乙型肝炎(乙肝)疫苗(Chinese hamster ovary cell derived hepatitis B vaccine,HepB-CHO)接种后18-20年免疫持久性和回忆反应。方法2017年10-11月在河北省正定县整群抽取1997-1999年出生且接种3剂次HepB-CHO...目的评价中国仓鼠卵巢细胞乙型肝炎(乙肝)疫苗(Chinese hamster ovary cell derived hepatitis B vaccine,HepB-CHO)接种后18-20年免疫持久性和回忆反应。方法2017年10-11月在河北省正定县整群抽取1997-1999年出生且接种3剂次HepB-CHO的受试者开展问卷调查,采用化学发光法检测血清乙肝表面抗原(Hepatitis B surface antigen,HBsAg)、表面抗体(Hepatitis B surface antibody,HBsAb)和核心抗体(Hepatitis B core antibody,HBcAb),分析乙肝病毒标志物阳性率和HBsAb几何平均浓度(Geometric mean concentration,GMC);随机选择HBsAb和其他标志物均阴性的受试者,随机分为两组分别加强接种1剂次HepB-CHO和酵母细胞乙肝疫苗(Yeast cell derived HepB,HepB-Y),检测接种后30d血清HBsAb,比较抗体阳转率和GMC。结果在1352例受试者中,3剂次HepB-CHO接种后18-20年HBsAg、HBsAb和HBcAb阳性率分别为0.4%(6例)、74.5%(1007例)和1.3%(18例),HBsAb阳性者HBsAb GMC为191mIU/mL。本次调查中HBsAg阳性者在2005年、2009年和2013年调查中均为阳性;4次调查显示同一队列的受试者HepB-CHO初次免疫后6-20年HBsAg、HBcAb和HBsAb阳性率未呈显著上升或下降趋势(趋势检验:χ^(2)=3.58,P>0.05;χ^(2)=3.42,P>0.05;χ^(2)=4.54,P>0.05)。248例HBsAb阴性受试者加强1剂次HepB-CHO或HepB-Y后HBsAb总阳转率为93.1%(231例),阳转者GMC为369mIU/mL;其中HepB-CHO、HepB-Y加强免疫受试者HBsAb阳转率分别为97.7%、88.3%(χ^(2)=8.43,P<0.05),阳转者GMC分别为578mIU/mL、226mIU/mL(t=7.16,P<0.05)。结论HepB-CHO初次免疫后18-20年具有良好的免疫持久性和回忆反应,提示普通人群无必要加强免疫。展开更多
The French National Immunization Program was updated in 2013 for vaccination against diphtheria,tetanus,per-tussis,and poliomyelitis.Our previous findings on the evolution of age-specific booster vaccination coverage ...The French National Immunization Program was updated in 2013 for vaccination against diphtheria,tetanus,per-tussis,and poliomyelitis.Our previous findings on the evolution of age-specific booster vaccination coverage rates(VCRs)up to 2017 suggested suboptimal vaccination coverages due to the pre-2013 recommendation-residual vaccination practices.In the current analysis,we evaluated all age-specific booster VCR and distribution of age at vaccination visits in 2018.In this retrospective observational cohort study,the cumulative booster VCRs were updated at all vaccination visits up to 2018 among the people who were eligible for a booster vaccination,using a 1/97th random sample of French national healthcare reimbursement databases.The cumulative booster VCR for individuals from all age groups increased from 2017 to 2018,except for 85-years-old vaccination visit.Majority of the individuals from all age groups were vaccinated(boosted)with a vaccine containing the pertussis valence.In 2018,sharp peaks corresponding to the recommended ages for booster vaccination visits were observed for individuals aged 6,11 to 13,25,45,and 65 years.Our study reiterates suboptimal coverages in France and implies the need for booster vaccination throughout life for the protection of the population.展开更多
目的观察新型冠状病毒疫苗加强免疫的免疫原性及安全性。方法2020年10月,江苏省疾病预防控制中心(CDC)开展了新型冠状病毒灭活疫苗的Ⅱ期临床试验,入组对象为18~59岁、未妊娠、未哺乳的健康人群,基础免疫程序为0-14 d 5μg、0-14 d 10μ...目的观察新型冠状病毒疫苗加强免疫的免疫原性及安全性。方法2020年10月,江苏省疾病预防控制中心(CDC)开展了新型冠状病毒灭活疫苗的Ⅱ期临床试验,入组对象为18~59岁、未妊娠、未哺乳的健康人群,基础免疫程序为0-14 d 5μg、0-14 d 10μg、0-28 d 5μg、0-28 d 10μg,从其中按研究编号从小到大顺序各选择50名(共200名)完成2剂基础免疫的受试者,在完成基础免疫后第6个月(窗口期30 d)加强接种第3剂与基础免疫同样剂量的疫苗。加强免疫前后分别采集静脉血约5 ml,分析活病毒中和抗体、假病毒中和抗体、受体结合域IgG抗体(RBD-IgG)的阳转率和几何平均滴度(GMT)。收集并分析加强免疫后28 d内不良事件发生情况。结果0-14 d 5μg、0-14 d 10μg、0-28 d 5μg、0-28 d 10μg组对象的基线年龄分别为(43.98±9.58)、(43.46±9.34)、(42.56±9.08)和(43.94±11.05)岁(P=0.877),各组间性别比例均衡(P=0.331);4组活病毒中和抗体GMT(95%CI)由加强免疫前的4.07(3.30~5.04)、3.75(3.08~4.55)、8.33(7.01~11.11)和7.69(6.19~9.57)升至加强免疫后28 d的284.84(215.28~376.86)、233.05(178.61~304.08)、274.81(223.64~337.68)和280.77(234.59~336.04),抗体阳转率均为100%。4组的加强免疫后28 d内不良事件发生率分别为18.0%(9例)、4.0%(2例)、12.0%(6例)和12.0%(6例)(P=0.182),无3级及以上不良事件、无严重不良事件。结论新型冠状病毒灭活疫苗基础免疫6个月后进行1剂加强免疫具有良好的免疫原性和安全性。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
目的评价儿童A群C群脑膜炎球菌多糖结合疫苗(Group A and C meningococcal polysaccharide conjugate vaccine,MPCV-AC)加强免疫的安全性和免疫原性。方法在前期完成MPCV-AC基础免疫Ⅲ期临床试验的受试者中,选择已于3月龄开始接种3剂MPC...目的评价儿童A群C群脑膜炎球菌多糖结合疫苗(Group A and C meningococcal polysaccharide conjugate vaccine,MPCV-AC)加强免疫的安全性和免疫原性。方法在前期完成MPCV-AC基础免疫Ⅲ期临床试验的受试者中,选择已于3月龄开始接种3剂MPCV-AC(A组)和已于6-11月龄开始接种2剂MPCV-AC(B组)的儿童,于18月龄时加强接种1剂MPCV-AC,观察接种后0-30d不良反应和6个月内严重不良反应,检测接种前后血清A群和C群脑膜炎奈瑟菌(Neisseria meningitidis,Nm)杀菌抗体,分析不良反应发生率、抗体阳性率和几何平均滴度(Geometric mean titer,GMT)。结果A组和B组受试者MPCV-AC加强免疫后不良反应发生率分别为22.5%(27/120)、25.8%(31/120),未发生4级不良反应和与疫苗接种有关的严重不良事件。A组受试者加强免疫后vs加强免疫前A群、C群Nm抗体阳性率分别为100%(112/112)vs 19.33%(23/119)、99.11%(111/112)vs 23.53%(28/119),GMT(1:)分别为877.21 vs 2.34、855.77 vs 2.25;B组受试者加强免疫后vs加强免疫前A群、C群Nm抗体阳性率分别为100%(112/112)vs 51.67%(62/120)、96.43%(108/112)vs 45.00%(54/120),GMT(1:)分别为466.61 vs 9.51、298.84 vs 5.31。结论完成MPCV-AC基础免疫的婴儿于18月龄加强免疫显示良好的安全性和免疫原性。展开更多
目的评估新型冠状病毒灭活疫苗免疫人群和小鼠血清对变异株(Delta株和Beta株)的交叉中和活性。方法各取20份人群常规两剂基础免疫血清、三剂加强免疫血清和两剂小鼠免疫血清作为实验材料,采用新型冠状病毒原型株、Delta和Beta变异株3株...目的评估新型冠状病毒灭活疫苗免疫人群和小鼠血清对变异株(Delta株和Beta株)的交叉中和活性。方法各取20份人群常规两剂基础免疫血清、三剂加强免疫血清和两剂小鼠免疫血清作为实验材料,采用新型冠状病毒原型株、Delta和Beta变异株3株病毒,在生物安全三级实验室中采用微量中和试验检测中和抗体。通过分析不同稀释度血清对固定剂量病毒的中和活性,计算血清阳性率和抗体几何平均滴度(geometric mean titer,GMT),评估免疫血清的交叉中和水平。结果人免疫血清对不同变异株的阳性率均大于95%;基础免疫后,接种者血清对原型株、Delta和Beta变异株的中和抗体GMT分别为109、41和15,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.7倍和7.3倍;加强免疫后,接种者血清对原型株、Delta和Beta株的中和抗体GMT分别为446、190和86,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.3倍和5.2倍。小鼠免疫血清对不同变异株的阳性率均为100%;对原型株、Delta和Beta变异株的中和抗体GMT分别为2037、862和408,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.4倍和5.0倍。结论新型冠状病毒灭活疫苗免疫后的人群和小鼠血清均可对Delta和Beta变异株产生一定水平的中和保护,且人群加强免疫后可产生更高水平的中和抗体和交叉中和抗体,为该疫苗的临床应用和保护效果评估提供了重要参考。展开更多
文摘自新冠疫情暴发以来,新冠病毒不断进化,Omicron作为第五个世界卫生组织公布的值得关注的变异株(variants of concern,VOCs),在基因组学、生物学以及流行病学特征上与之前的VOCs存在明显差异。虽然Omicron感染导致的重症率和死亡率相对其他VOCs明显下降,但其极强的传播力不断突破既往感染和疫苗建立的人群免疫屏障和防疫壁垒,可以说Omicron揭开了新冠疫情防控的新篇章。本文对Omicron变异株及其亚种的基因组学、生物学、流行病学特征及其与流感病毒的差异进行阐述,以期为优化疫情防控策略提供科学依据。
文摘目的观察甲型肝炎(甲肝)减毒活疫苗(Hepatitis A Attenuated Live Vaccine,HepA-L)不同免疫程序免疫后7年的抗体持久性,并与甲肝灭活疫苗(Hepatitis A Inactivated Vaccine,HepA-I)进行比较。方法按个体随机的方法,把筛检出的甲肝易感者随机分为A、B、C三组。A组按0、6、12个月程序接种3剂国产H2株HepA-L,B、C两组按0、6个月程序分别接种HepA-L和HepA-I,分别于免疫后1、6、7、12、13、24、84个月采集血清标本,检测抗甲肝病毒抗体(Anti-hepatitis A Virus Antibody,Anti-HAV)总抗体。结果三组Anti-HAV阳性率均于接种第2剂后1个月达100%,抗体峰值几何平均浓度(Geometric Mean Concentration,GMC)以C组最高,为2938.1mIU/ml(毫国际单位/毫升),A、B组分别为1315.6mIU/ml、1586.0mIU/ml。A组于12个月时再加强免疫1剂,抗体GMC上升,达1945.3mIU/ml。首剂免疫后84个月,Anti-HAV阳性率三组均保持100%,尽管A组抗体GMC降至336.8mIU/ml,仍显著高于B、C两组。结论HepA-L近期加强免疫效果良好,抗体反应与持久性同HepA-I相当,远期效果有待于进一步观察。
基金supported by Beijing Natural Science Foundation(No.L222068 to Bin Su)the National Natural Science Foundation of China(NSFC,No.82272319 to Hu Wu,and No.81974303 to Bin Su)+3 种基金the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(No.2022-2-018 to Bin Su,and No.2022-1-007 to Tong Zhang)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(No.DFL20191701 to Tong Zhang)the Beijing Health Technologies Promotion Program(No.BHTPP202002 to Tong Zhang)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).
文摘Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor activity.However,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated vaccines.Methods:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this study.The amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third dose.Results:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in PLWH.Interestingly,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay.Compared with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs.Additionally,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T cells.However,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was insignificant at 4W and 12W,except at 0W.Conclusi
文摘目的评价中国仓鼠卵巢细胞乙型肝炎(乙肝)疫苗(Chinese hamster ovary cell derived hepatitis B vaccine,HepB-CHO)接种后18-20年免疫持久性和回忆反应。方法2017年10-11月在河北省正定县整群抽取1997-1999年出生且接种3剂次HepB-CHO的受试者开展问卷调查,采用化学发光法检测血清乙肝表面抗原(Hepatitis B surface antigen,HBsAg)、表面抗体(Hepatitis B surface antibody,HBsAb)和核心抗体(Hepatitis B core antibody,HBcAb),分析乙肝病毒标志物阳性率和HBsAb几何平均浓度(Geometric mean concentration,GMC);随机选择HBsAb和其他标志物均阴性的受试者,随机分为两组分别加强接种1剂次HepB-CHO和酵母细胞乙肝疫苗(Yeast cell derived HepB,HepB-Y),检测接种后30d血清HBsAb,比较抗体阳转率和GMC。结果在1352例受试者中,3剂次HepB-CHO接种后18-20年HBsAg、HBsAb和HBcAb阳性率分别为0.4%(6例)、74.5%(1007例)和1.3%(18例),HBsAb阳性者HBsAb GMC为191mIU/mL。本次调查中HBsAg阳性者在2005年、2009年和2013年调查中均为阳性;4次调查显示同一队列的受试者HepB-CHO初次免疫后6-20年HBsAg、HBcAb和HBsAb阳性率未呈显著上升或下降趋势(趋势检验:χ^(2)=3.58,P>0.05;χ^(2)=3.42,P>0.05;χ^(2)=4.54,P>0.05)。248例HBsAb阴性受试者加强1剂次HepB-CHO或HepB-Y后HBsAb总阳转率为93.1%(231例),阳转者GMC为369mIU/mL;其中HepB-CHO、HepB-Y加强免疫受试者HBsAb阳转率分别为97.7%、88.3%(χ^(2)=8.43,P<0.05),阳转者GMC分别为578mIU/mL、226mIU/mL(t=7.16,P<0.05)。结论HepB-CHO初次免疫后18-20年具有良好的免疫持久性和回忆反应,提示普通人群无必要加强免疫。
文摘The French National Immunization Program was updated in 2013 for vaccination against diphtheria,tetanus,per-tussis,and poliomyelitis.Our previous findings on the evolution of age-specific booster vaccination coverage rates(VCRs)up to 2017 suggested suboptimal vaccination coverages due to the pre-2013 recommendation-residual vaccination practices.In the current analysis,we evaluated all age-specific booster VCR and distribution of age at vaccination visits in 2018.In this retrospective observational cohort study,the cumulative booster VCRs were updated at all vaccination visits up to 2018 among the people who were eligible for a booster vaccination,using a 1/97th random sample of French national healthcare reimbursement databases.The cumulative booster VCR for individuals from all age groups increased from 2017 to 2018,except for 85-years-old vaccination visit.Majority of the individuals from all age groups were vaccinated(boosted)with a vaccine containing the pertussis valence.In 2018,sharp peaks corresponding to the recommended ages for booster vaccination visits were observed for individuals aged 6,11 to 13,25,45,and 65 years.Our study reiterates suboptimal coverages in France and implies the need for booster vaccination throughout life for the protection of the population.
文摘目的观察新型冠状病毒疫苗加强免疫的免疫原性及安全性。方法2020年10月,江苏省疾病预防控制中心(CDC)开展了新型冠状病毒灭活疫苗的Ⅱ期临床试验,入组对象为18~59岁、未妊娠、未哺乳的健康人群,基础免疫程序为0-14 d 5μg、0-14 d 10μg、0-28 d 5μg、0-28 d 10μg,从其中按研究编号从小到大顺序各选择50名(共200名)完成2剂基础免疫的受试者,在完成基础免疫后第6个月(窗口期30 d)加强接种第3剂与基础免疫同样剂量的疫苗。加强免疫前后分别采集静脉血约5 ml,分析活病毒中和抗体、假病毒中和抗体、受体结合域IgG抗体(RBD-IgG)的阳转率和几何平均滴度(GMT)。收集并分析加强免疫后28 d内不良事件发生情况。结果0-14 d 5μg、0-14 d 10μg、0-28 d 5μg、0-28 d 10μg组对象的基线年龄分别为(43.98±9.58)、(43.46±9.34)、(42.56±9.08)和(43.94±11.05)岁(P=0.877),各组间性别比例均衡(P=0.331);4组活病毒中和抗体GMT(95%CI)由加强免疫前的4.07(3.30~5.04)、3.75(3.08~4.55)、8.33(7.01~11.11)和7.69(6.19~9.57)升至加强免疫后28 d的284.84(215.28~376.86)、233.05(178.61~304.08)、274.81(223.64~337.68)和280.77(234.59~336.04),抗体阳转率均为100%。4组的加强免疫后28 d内不良事件发生率分别为18.0%(9例)、4.0%(2例)、12.0%(6例)和12.0%(6例)(P=0.182),无3级及以上不良事件、无严重不良事件。结论新型冠状病毒灭活疫苗基础免疫6个月后进行1剂加强免疫具有良好的免疫原性和安全性。
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.
文摘目的评价儿童A群C群脑膜炎球菌多糖结合疫苗(Group A and C meningococcal polysaccharide conjugate vaccine,MPCV-AC)加强免疫的安全性和免疫原性。方法在前期完成MPCV-AC基础免疫Ⅲ期临床试验的受试者中,选择已于3月龄开始接种3剂MPCV-AC(A组)和已于6-11月龄开始接种2剂MPCV-AC(B组)的儿童,于18月龄时加强接种1剂MPCV-AC,观察接种后0-30d不良反应和6个月内严重不良反应,检测接种前后血清A群和C群脑膜炎奈瑟菌(Neisseria meningitidis,Nm)杀菌抗体,分析不良反应发生率、抗体阳性率和几何平均滴度(Geometric mean titer,GMT)。结果A组和B组受试者MPCV-AC加强免疫后不良反应发生率分别为22.5%(27/120)、25.8%(31/120),未发生4级不良反应和与疫苗接种有关的严重不良事件。A组受试者加强免疫后vs加强免疫前A群、C群Nm抗体阳性率分别为100%(112/112)vs 19.33%(23/119)、99.11%(111/112)vs 23.53%(28/119),GMT(1:)分别为877.21 vs 2.34、855.77 vs 2.25;B组受试者加强免疫后vs加强免疫前A群、C群Nm抗体阳性率分别为100%(112/112)vs 51.67%(62/120)、96.43%(108/112)vs 45.00%(54/120),GMT(1:)分别为466.61 vs 9.51、298.84 vs 5.31。结论完成MPCV-AC基础免疫的婴儿于18月龄加强免疫显示良好的安全性和免疫原性。
文摘目的评估新型冠状病毒灭活疫苗免疫人群和小鼠血清对变异株(Delta株和Beta株)的交叉中和活性。方法各取20份人群常规两剂基础免疫血清、三剂加强免疫血清和两剂小鼠免疫血清作为实验材料,采用新型冠状病毒原型株、Delta和Beta变异株3株病毒,在生物安全三级实验室中采用微量中和试验检测中和抗体。通过分析不同稀释度血清对固定剂量病毒的中和活性,计算血清阳性率和抗体几何平均滴度(geometric mean titer,GMT),评估免疫血清的交叉中和水平。结果人免疫血清对不同变异株的阳性率均大于95%;基础免疫后,接种者血清对原型株、Delta和Beta变异株的中和抗体GMT分别为109、41和15,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.7倍和7.3倍;加强免疫后,接种者血清对原型株、Delta和Beta株的中和抗体GMT分别为446、190和86,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.3倍和5.2倍。小鼠免疫血清对不同变异株的阳性率均为100%;对原型株、Delta和Beta变异株的中和抗体GMT分别为2037、862和408,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.4倍和5.0倍。结论新型冠状病毒灭活疫苗免疫后的人群和小鼠血清均可对Delta和Beta变异株产生一定水平的中和保护,且人群加强免疫后可产生更高水平的中和抗体和交叉中和抗体,为该疫苗的临床应用和保护效果评估提供了重要参考。
