b型流感嗜血杆菌结合疫苗接种后婴幼儿安全性和免疫原性研究

目的 评价b型流感嗜血杆菌结合疫苗(Hib-TT)安全性和免疫原性.方法 分别采用Hib-TT试验疫苗和对照疫苗3针免疫接种3～5月龄婴幼儿,观察疫苗安全性,并采用定量ELISA法分别测定免疫前、免疫后和加强免疫后血清特异性IgG抗体浓度.结果 实验疫苗和对照疫苗两组间不良反应总发生率(实验疫苗组为23.85％,对照疫苗组为31.40％)差异无统计学意义(x2=0.5,P＞0.05),发热性总不良反应率分别为22.3％和31.3％,中、强发热反应率分别为3.67％和4.48％,差异无统计学意义;实验疫苗受试者局部红、肿、硬结等不良反应率为1.22％.实验疫苗3剂免疫后受试者血清抗Hib PRP IgG抗体平均几何浓度(GMC)为6.6786 μg/ml,对照疫苗组血清抗体GMC为7.5346 μg/ml,两组间抗体GMC差异无统计学意义(x2=0.147,P=0.702);加强免疫1剂后,实验疫苗组受试者血清抗体GMC从加强免疫前的2.6396 μg/ml上升为6.2044μg/ml.结论 实验疫苗接种3～5月龄婴幼儿具有良好的安全性.用间隔1个月、3剂次接种的基础免疫程序能诱导该年龄组受试者产生长期保护水平的血清特异性抗体,加强免疫1剂后能诱导机体产生免疫记忆反应.     

EHF疫苗不同途径免疫后血清及黏膜抗体应答情况

目的探讨EHF疫苗经不同剂量和途径免疫后血清IgG及黏膜IgA产生情况,以探讨合适的免疫剂量和接种途径。方法以不同剂量EHF双价灭活疫苗分别经皮下和灌胃免疫小鼠,共3次（第0、5、10天）,末次接种后5d收集血清和小肠冲洗液,用间接免疫荧光法（IFA）检测血清EHF IgG抗体和小肠冲洗液IgA抗体。结果皮下注射能诱导血清特异性IgG和黏膜IgA的产生,灌胃免疫未见抗体产生,1．4 TCID50的EHF疫苗剂量在皮下注射组血清IgG和小肠冲洗液IgA有100％阳性率。结论EHF疫苗皮下注射能诱导血清特异性IgG和黏膜IgA的产生,1．4 TCID50的剂量为较佳剂量。     

狂犬病疫苗免疫后血清抗体水平的调查

狂犬病疫苗免疫后血清抗体水平的调查朱宝根，张晓娟，赵娟，傅晓琰我们用间接免疫荧光法（ＩＦＡ）检测了人血清狂犬病病毒ＩｇＧ抗体，分析了不同性别、年龄对狂犬病疫苗免疫效果的影响，并对免疫失败的原因进行了初步探讨。材料与方法１．标本来源暴露者狂犬病疫苗全程...     

质粒DNA促进HBsAg-抗HBs复合型疫苗诱生的免疫应答的研究

目的　研究HBsAg 抗HBs 质粒DNA复合型疫苗的免疫原性及其诱生细胞免疫应答的类型。方法　分别以HBsAg、HBsAg 抗 HBs(IC)、pI/AmpHBs、IC pI/AmpHBs及IC pI/Amp免疫小鼠 ,检测抗 HBs的效价 ,分析抗 HBsIgG亚类 (ELISA) ;取免疫小鼠脾细胞 ,体外抗原刺激 ,用竞争性RT PCR方法检测IFN γ及IL 4mRNA转录水平。结果　IC pI/AmpHBs诱生的抗 HBs效价明显高于IC或pI/AmpHBs单独免疫组 ,其IgG2a/IgG1比值高于IC免疫组 ,而低于pI/AmpHBs免疫组。IC pI/AmpHBs免疫小鼠脾细胞在HBsAg刺激下 ,IFN γmRNA转录水平明显高于其他免疫组 ,其IFN γmRNA的T/C(目的片段Target/竞争片段Competitor)比值为IC免疫小鼠脾细胞的 10倍 ;IC pI/AmpHBs免疫小鼠脾细胞IL 4mRNA转录水平亦高于其他免疫组 ,其IL 4mRNA的T/C比值为IC免疫小鼠脾细胞的 2倍。结论　HBsAg 抗HBs 质粒DNA复合型疫苗在增强体液免疫应答的同时可诱导脾细胞IFN γ的表达水平增高。     

双价志贺疫苗滴鼻免疫小鼠后粘膜免疫与系统免疫应答持续时间的观察

本文探讨双价志贺疫苗滴鼻免疫小鼠一段时间后,粘膜免疫和系统免疫应答的变化。将BALB/c小鼠随机分为三组,每组30只。PBS、FSM-2117和FS-5416(菌量为5×10~6、1×10~7、4×10~7和4×10~7CFU/只/次)经滴鼻途径免疫小鼠。间隔2周,4次免疫后7、30和90d活杀,收集鼻咽、肺、肠、生殖道冲洗液和血清。采用ELISA法检测其中特异性抗福氏、宋内LPSIgA和IgG。结果是两株疫苗经鼻内免疫后,诱发鼻咽、肺、胃肠道和生殖道等不同粘膜部位及血清中特异性抗福氏、宋内LPSIgA、IgG的显著增加(P<0.01)。特异性抗体水平虽然在免疫后30、90d明显下降,但仍明显高于PBS对照组水平。故认为两株双价志贺疫苗滴鼻免疫小鼠后能有效诱导粘膜免疫和系统免疫应答,并持续较长时间。     

正常人血清中IgG类抗角蛋白自身抗体的免疫印迹分析

抗角蛋白自身抗体是正常人天然自身抗体的一部分。本研究用一组角蛋白对正常人血清中的ＩｇＧ 类抗角蛋白抗体进行了免疫印迹分析。２１ 份正常人血清均可识别至少一种角蛋白成分， 可区分出１４ 种反应性模式。３ 份合并血清的反应性模式高度均一。结果表明， 血清抗角蛋白抗体普遍存在， 但在人群中呈高度异质性； 不同个体血清可互补。角蛋白 抗角蛋白系统可能是天然自身抗体研究的一个理想模式系统。     

免疫复合物型乙型肝炎疫苗的免疫原性分析北大核心CSCD

目的：分析免疫复合物型乙型肝炎疫苗在小鼠体内和食蟹猴体内的免疫原性。方法免疫复合物型乙型肝炎疫苗单次免疫小鼠,不同时间点采血进行anti-HBs滴度动态检测;不同免疫程序免疫小鼠,进行anti-HBs滴度检测;肌肉注射5μg/只免疫小鼠,ELISPOT方法检测IFN-γ形成斑点数并进行阳转率统计;测定稳定性试验样品的ED50;分别以20μg/只和100μg/只剂量免疫食蟹猴,不同时间点采血检测anti-HBs滴度。结果免疫复合物型乙型肝炎疫苗动态检测anti-HBs滴度均高于重组乙型肝炎疫苗（酿酒酵母）;免疫复合物型乙型肝炎免疫2针次anti-HBs滴度可达到重组乙型肝炎疫苗（酿酒酵母）免疫3针次水平;免疫复合物型乙型肝炎疫苗细胞免疫检测IFN-γ斑点形成细胞（ SFC）及阳转率高于重组乙型肝炎疫苗（酿酒酵母）及酿酒乙型肝炎疫苗国家参考品;免疫复合物型乙型肝炎疫苗长期稳定性优于酿酒酵母乙肝疫苗,ED50值低于后者,高低两种剂量免疫食蟹猴,均可诱导高滴度anti-HBs,且持续性良好。结论免疫复合物型乙型肝炎疫苗有较好的免疫原性,其体液免疫和细胞免疫水平均优于重组乙型肝炎疫苗（酿酒酵母）。     

西藏自治区健康人群接种新型冠状病毒肺炎疫苗后特异性IgG抗体调查

目的了解西藏自治区健康人群在新型冠状病毒肺炎(Coronavirus Disease 2019, COVID-19)灭活疫苗免疫后的新型冠状病毒(2019 novel coronavirus, 2019-nCoV)特异性IgG抗体阳性率, 评价疫苗免疫效果。方法从西藏自治区6个地级市选择无2019-nCoV感染史并已完成全程2剂次免疫或加强免疫的健康人群作为研究对象, 采集血清样本并用化学发光法检测2019-nCoV特异性IgG抗体, 分析不同免疫史以及各年龄组接种者的抗体阳性率。结果共计纳入调查对象22 255名, 2019-nCoV特异性IgG抗体总体阳性率为96.38%。加强免疫人群的抗体阳性率为97.12%, 远高于全程免疫人群的88.38%, 差异具有统计学意义(χ2=381.11,P<0.001)。不同年龄组间抗体阳性率差异有统计学意义(χ2=138.28,P<0.001), 低年龄≤10岁和11～20岁组的抗体阳性率均低于其他年龄组, 分别为93.44%和89.03%。除那曲市和≤10岁年龄组外, 同地区不同年龄组之间和不同地区相同年龄组之间的不同免疫史人群抗...     

乙型肝炎疫苗加强接种2年后的免疫应答

<正> 我们曾报道对乙型肝炎疫苗(下简称乙肝疫苗)初免3年抗-HBs呈低水平(S/N≤5)和转阴的儿童,加强注射1剂10μg或30μg乙肝疫苗,取得快而好的回忆反应,本文报道加强免疫2年后受检查者抗-HBs水平及保护力的观察结果。 材料和方法 观察对象的选择和分组均见前报,新生儿(3岁)组随机分成二组,分别加强接种1剂10μg或30μg乙肝疫苗,儿童(4～8岁)组     

IgG型抗E抗体联合IgG型抗Fyb抗体的血清学检测分析

目的 分析IgG型抗E抗体联合IgG型抗Fyb抗体的血清学检测结果及配血对策.方法 对患者血标本进行ABO及Rh血型鉴定和不规则抗体筛选,对抗体筛选阳性血标本采用盐水法、间接抗人球蛋白法进行抗体特异性鉴定.确定抗体特异性后,再用抗人球蛋白法检测红细胞是否含有相应抗原;采用盐水法、凝聚胺法及间接抗人球蛋白法进行交叉配血试...     

Divergent serotype distribution between children with otitis media and those without in the pneumococcal conjugate vaccine era

We investigated pneumococcal carriage between children ≦5 years old with otitis media (OM) and those without. Non-PCV13 serotypes were common in both groups; 19A remained the second most common serotype among children with OM despite high PCV13 coverage. This is important when considering a schedule with reduced vaccine doses or reduced valency, and the modification of pneumococcal immunization schedule should be followed up closely to monitor the result of protection against pneumococcal infections.     

vUTAL3CP1重组载体疫苗与pVIRIL18P1 DNA疫苗在猪体内的免疫原性研究

目的 评价本课题组构建的共表达FMDV衣壳蛋白前体P1-2A基因以及免疫辅助基因的重组鸡痘病毒vUTAL3CP1和重组DNA疫苗pVIRIL18P1在猪体内诱导特异性体液免疫和细胞免疫的能力。方法将上述2种疫苗采用4种不同的组合方式单独或联合给猪进行肌肉注射,用ELISA方法和中和实验检测猪产生的抗体水平,T淋巴细胞增殖反应、CTL反应以及T淋巴细胞亚类。结果这2种基因工程疫苗均能诱导猪产生特异性的体液及细胞免疫应答。其中单独免疫组vUTAL3CP1/vUTAL3CP1的效果最好,其诱导的抗体水平已接近于常规灭活疫苗,而细胞免疫水平则比后者高得多。联合免疫组中vUTAL3CP1／pVIRIL18P1可以诱导比vUTAL3CP1,vUTAL3CP1更高的CTL杀伤活性,但体液免疫水平略低。结论证实了这2种基因工程疫苗在猪体内均有良好的免疫原性。同时初步筛选出vUTAL3CP1/vUTAL3CP1和pVIRIL18P1／vUTAL3CP1组等较佳的免疫策略,为下一步的攻毒保护试验奠定了基础。     

The kinetics and phenotype of the human B-cell response following immunization with a heptavalent pneumococcal-CRM conjugate vaccine

Primary immunization of infants with protein-polysaccharide conjugate vaccines induces antipolysaccharide antibody and is highly effective in preventing invasive disease caused by encapsulated bacteria. However, recent experience from the UK indicates that this immunity is not sustained in the absence of booster doses of vaccine. This study aimed to establish the kinetics and phenotype of B-cell subpopulations responding to booster immunization with a heptavalent pneumococcal conjugate vaccine (Pnc7), which is to be introduced into the primary immunization schedule in the UK during 2006. Six adult volunteers received a booster dose of Pnc7 12-18 months after primary immunization. CD27hi CD38hi CD20(+/-) IgG antibody-forming cells were detected in peripheral blood with maximum frequency at days 6-7 after immunization. This was accompanied by a more prolonged rise in memory B cells that required in vitro stimulation with Staphylococcus aureus Cowan strain and interleukin-2 to induce antibody secretion. These data provide evidence for at least two subsets of antibody-forming cells involved in the secondary humoral response to a glycoconjugate vaccine in primed individuals. A briefly circulating subset of B cells that spontaneously secrete immunoglobulin G may be responsible for early defence against re-encountered encapsulated bacteria. However, the kinetics of the appearance of these cells may indicate that the humoral immune response is too slow in defence against an organism that invades within days of acquisition. The more sustained presence of a memory population may provide persistence of antipolysaccharide antibody after a booster dose of vaccine and may also include re-circulatory populations responsible for further anamnestic responses.     

Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) in children and adults

Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain the only practical means to reduce significantly the remaining global mortality and morbidity due to S. pneumoniae in adults.     

Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection

Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8–69 months and 15 carefully age-matched healthy controls once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG 1–4 specificity were determined by ELISA. There were no significant differences between the two groups in any single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls ( P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls ( P = 0.005), whereas 1 month later they had significantly more IgM antibody (P = 0.038). No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies. Since naturally occurring IgG antibodies are thought to be aquired partly as a consequence of antigenic stimulation on mucosal surfaces, we hypothesize that the low level of specific IgG found before immunization, as well as the low total IgG in the children with RLRI, may reflect an impaired ability to prime through mucosal surfaces. This is supported by our finding of an increased IgM response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory. In conclusion, children with RLRI can be protected against invasive Hib infection as well as healthy children, but may have an immunodeficiency characterized by defective ability to respond to antigenic stimulation on mucosal surfaces.     

空肠弯曲菌pcDNA3.1(-)-peb1A壳聚糖佐剂疫苗对小鼠免疫原性和保护性研究

目的:研究空肠弯曲菌pcDNA3.1(-)-peb1A壳聚糖佐剂疫苗的免疫原性和保护性。方法:健康雄性昆明小鼠分为实验组和对照组。实验组设pcDNA3.1(-)-peb1A组3个剂量和壳聚糖-pcDNA3.1(-)-peb1A组3个剂量;对照组设空载体pcDNA3.1(-)(100μg/100μl)组和生理盐水(NS)组,各组均采用小鼠股四头肌注射法。在第0、10、20天免疫,于每次免疫后第10天采集各组小鼠血清,以间接ELISA法检测血清中特异性IgM、IgG的含量。分离各组小鼠脾淋巴细胞包被细胞培养板,以细胞ELISA法检测小鼠脾淋巴细胞CD20、CD21表达水平。设空肠弯曲菌液灌胃攻击免疫后小鼠,检测肠道分泌液细菌培养数量。结果:裸DNA组和壳聚糖-DNA组各组特异性IgG水平均高于两对照组(P<0.05)。裸DNA组和壳聚糖-DNA组小鼠脾淋巴细胞CD20、CD21表达水平均高于两对照组(P<0.05),壳聚糖-DNA组高于裸DNA组(P<0.05)。肠道分泌液细菌培养结果细菌指数裸DNA组的低于两对照组;佐剂DNA组低于裸DNA组。结论:重组质粒pcDNA3.1(-)-peb1A经肌肉注射免疫小鼠,具有较好的免疫原性和保护作用,壳聚糖能增强pcDNA3.1(-)-peblA的免疫原性,有望成为空肠弯曲菌基因疫苗的候选佐剂。     

Immunogenicity of a fourth dose of Haemophilus influenzae type b (Hib) conjugate vaccine and antibody persistence in young children from the United Kingdom who were primed with acellular or whole-cell pertussis component-containing Hib combinations in infancy

In response to the rising incidence of Haemophilus influenzae type b (Hib) disease in the United Kingdom, a national campaign to give a booster dose of single-antigen Hib conjugate vaccine to children aged 6 months to 4 years was undertaken in 2003. Children (n = 386) eligible for Hib vaccine in the campaign were recruited. Hib antibody concentrations were measured before boost and at 1 month, 6 months, 1 year, and 2 years after boost and were analyzed according to children's ages at booster dose and whether a Hib combination vaccine containing acellular pertussis (aP) or whole-cell pertussis (wP) components was given in infancy. The geometric mean antibody concentrations (GMCs) before the booster declined as the time since primary immunization increased (P < 0.001), and GMCs were threefold higher in recipients of wP-Hib than aP-Hib combination vaccines (P < 0.001). GMCs 1 month after the booster increased with age (P < 0.001) as follows: 6 to 11 months; 30 microg/ml (95% confidence interval [CI], 22 to 40); 12 to 17 months, 68 microg/ml (95% CI, 38 to 124); and 2 to 4 years, 182 microg/ml (151 to 220), with no difference according to the type of priming vaccine received. Antibody levels declined after the booster, but 2 years later, GMCs were more than 1.0 microg/ml for all age groups. By extrapolating data for the decline in antibody levels, we found the GMCs 4 years after boosting were predicted to be 0.6, 1.4, and 2.6 microg/ml for those boosted at 6 to 11 months, 12 to 17 months, and 2 to 4 years, respectively, with levels of at least 0.15 microg/ml in about 90% of individuals. A booster dose of Hib vaccine given after the first year of life should provide long-lasting protection.     

Immunogenicity of, and immunologic memory to, a reduced primary schedule of meningococcal C-tetanus toxoid conjugate vaccine in infants in the United kingdom

It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one- or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n = 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10- micro g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of > or =8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of > or =8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.