重组(汉逊酵母)乙型肝炎疫苗副反应和抗体应答观察

观察重组(汉逊酵母)乙肝疫苗免疫儿童的副反应和抗体应答。按0、1、6月免疫程序,分别应用2批重组汉逊酵母疫苗和2批重组酿酒酵母疫苗,免疫221名6至12岁儿童,其中汉逊酵母疫苗1批(A)接种102人,另一批(B)接种26人,重组酿酒酵母疫苗1批(C)和另1批(D)分别接种74和19人。观察每次接种后的副反应和全程免疫一月后(T7)的抗体应答。儿童接种汉逊酵母疫苗后副反应发生率低,有个别出现发热反应,但均低于37.8℃,且为一过性。T7时4组儿童抗HBs血清阳转率均在96%以上,GMT范围在229.98～338.83IU/L之间。免疫A批疫苗儿童组抗体滴度(GMT)显著高于免疫C批疫苗组(270.33、229.98IU/L;P<0.05)。汉逊酵母乙肝疫苗具有较好的安全性,免疫儿童抗体应答水平较高。     

儿童2剂水痘疫苗不同间隔免疫程序的比较

目的了解水痘疫苗2剂不同间隔时间免疫程序的安全性及免疫原性。方法按照随机、双盲的原则,选择符合条件的1~3岁、4~6岁、7~12岁儿童各200名,每个年龄组按照2剂间隔3个月和6个月的免疫程序,分别接种2剂冻干水痘减毒活疫苗。观察各组接种后的不良反应率,用膜抗原荧光抗体法(FAMA)检测疫苗接种前、后血清抗体阳转率、GMT水平和平均增长倍数。结果接种2剂水痘疫苗后,总体不良反应率在4%~13%;同年龄组不同间隔时间接种2剂疫苗后,不良反应发生率差异无统计学意义;不同年龄组间不良反应发生率差异无统计学意义。同年龄组不同间隔时间免前及接种2剂后,血清GMT水平差异均无统计学意义;同年龄组接种1剂与2剂水痘疫苗的血清GMT水平,两者间差异有显著性统计学意义。接种2剂水痘疫苗的GMT增长倍数高于接种1剂。不同间隔时间接种第2剂水痘疫苗后抗体阳转率差异无统计学意义;同年龄组接种2剂后抗体阳转率高于接种1剂,两者差异有统计学意义。结论间隔3个月和6个月接种第2剂水痘疫苗,在安全性及免后GMT水平、增长倍数及抗体阳转率等4个方面,两者差异均无统计学意义。     

流感病毒裂解疫苗临床安全性和免疫原性研究

目的了解流感病毒裂解疫苗的安全性和免疫原性。方法按整群随机抽样原则,对上海市200名18~60岁健康成人进行疫苗接种后临床安全性指标(局部反应、全身反应)的监测。用微量血凝抑制试验检测血清HI抗体,比较血清抗体阳转率、抗体几何平均滴度(GMT)和增长倍数。结果接种疫苗72 h内局部反应率为7.00%;全身反应率为12.00%,其中发热反应率为7.50%,其他全身反应率为4.50%;均以轻度反应为主。H1N1、H3N2和B型免疫后抗体阳转率分别为63.49%、74.07%和56.08%,抗体GMT分别为1∶170.10、1∶128.85和1∶446.79,免疫后比免疫前分别增长到6.93倍、8.72倍和4.90倍。结论此流感病毒裂解疫苗的临床安全性和免疫原性均较好。     

麻疹、腮腺炎、风疹三联减毒活疫苗的安全性和免疫原性研究

为了评价国产麻疹、腮腺炎、风疹三联减毒活疫苗(MMR)的安全性和免疫原性,按整体随机抽样原则,以进口同类疫苗和国产各单价疫苗作为对照,开展现场临床观察;比较不同疫苗组免疫后的反应率、抗体阳转率、保护率及几何平均滴度(GMT)。试验组与对照组接种后,除了试验疫苗的中、强发热反应率高于进口对照疫苗的发热反应率(8.60%与2.00%)外,未见其它有显著差异的不良反应。试验组麻疹免后抗体阳转率高于进口对照疫苗(99.5%与94.6%),麻疹抗体GMT也高于单价麻疹对照疫苗的GMT;试验疫苗与进口MMR疫苗的风疹抗体阳转率、腮腺炎抗体阳转率相比,均无显著性差异。实验研究结果显示,试验MMR疫苗与进口MMR疫苗具有相似的临床反应及良好的免疫原性。     

建立膜抗原荧光抗体试验评价北京株冻干水痘疫苗免疫效果

为了建立用于水痘疫苗接种后血清中特异性抗体检测的膜抗原荧光抗体(FAMA)法,并对接种水痘疫苗后儿童血清中水痘特异性抗体进行检测,评价北京株水痘疫苗的免疫效果。以水痘带状疱疹病毒(VZV)感染细胞作为抗原制备成固定抗原玻片,以异硫氰酸荧光素(FITC)标记的羊抗人IgG作为二抗建立FAMA法,并对该法的敏感性、特异性进行验证。运用此法对不同剂量北京株水痘疫苗接种后儿童血清中特异性抗体进行检测,分析儿童血清中水痘特异性抗体水平以及免后抗体阳转率,并与Oka株水痘疫苗进行比较。结果显示,FAMA法敏感性可达0.0196IU/ml,特异性好。应用此法检测300名观察者免前免后双份血清样本中抗VZVIgG,易感者中北京株水痘疫苗原苗(39810PFU/0.5ml)、2000PFU/0.5ml、500PFU/0.5ml接种组儿童血清免后抗体阳转率分别为100%、98.77%、85.42%,抗体几何平均滴度(GMT)分别为36.4、34.3、18.6,原苗与2000PFU间的抗体阳转率和GMT均无显著性差异(P>0.05),但原苗与500PFU、2000PFU与500PFU间的抗体阳转率和GMT均有显著性差异(P<0.05)。对照国产、进口Oka株水痘疫苗接种后抗体阳转率分别为95.35%、96.97%,抗体GMT分别为13.3、16.0,不同剂量北京株疫苗抗体阳转率与国产、进口Oka株疫苗相比,差别无显著性(P>0.05),但北京株疫苗原?     

流行性感冒灭活疫苗人体免疫效果及评价

通过对兰州生物制品研究所试生产的流行性感冒灭活疫苗的体试验研究,兰州所流感灭活疫苗接种后,所有接种对象均未见红肿,硬结等局部反应,仅有1例发生在儿童组的低热全身反应（体温37．4℃）,72小时后恢复正常,整体副反应发生率0．274％,肯定了该疫苗的安全性,疫苗接种前后易人群血清血凝抑制（HI）抗体阳转率100％,非易感人群HI抗体几何平均效价（GMT）增长19－60倍,抗体4倍增长率最低为95％,成人组平均值最高（97．67％）,证实该疫苗具有较好的免疫原性。     

地鼠肾原代细胞双价肾综合征出血热疫苗免疫效果的研究

对新近研制成功的地鼠肾原代细胞肾综合征出血热双价疫苗（汉滩型＋汉城型）进行了Ⅱ期临床扩大观察,考核其对人体的安全性和中和抗体反应。将观察人群分别选择在中国南方和北方两个点,每个点接种589人和600人,观察其接种对象的副反应程度和采集血清样品测定其光抗体并以蚀斑减少中和法测定中和抗体,考核疫苗效果。观察结果显示,在观察的253人中分别有6人呈现轻度局部副反应和1人37．5℃以下的低热全身反应,总反应率分别为2．77％（7／253）。IFAT抗体阳转率对I型病毒为94．85％（184／194）,对Ⅱ型病毒为89．69％（174／194）,ELISA抗体阳转率为99．44％（179／180）,GMT1325。PRNT抗体阳转率I型为92．55％（87／94）,GMT10．17,Ⅱ型为93．62％（88／94）,GMT11．08。经过Ⅱ期临床人体观察结果显示,该双价疫苗仅有轻度局部反应和良好的中和抗体应答。证明该疫苗对人体安全,具有较好的免疫原性。     

国产重组酵母乙型肝炎疫苗接种小学生的五年免疫效果观察

为了解国产重组酵母乙肝疫苗的免疫持久性,对接种2批国产酵母疫苗（5μg/Dose),1批进口酵母疫苗（A;10μg/Dose)和另1批进口酵母疫苗（M;5μg/Dose)的268名小学生,进行了免后5年（T60）效果随访观察。结果表明,T60时接种A疫苗组抗体GMT（几何平均滴度）（197．53）显著高于M疫苗组（110．66）和2批国产疫苗（9312645GMT78．48,9312623GMT56．06）。抗体阳转率A疫苗组（85．71％）显著高于M疫苗组及国产两批疫苗（61．76％、65．26％、63．83％）（P＜0．05）。而国产两批疫苗与M疫苗组无显著性差异（P＞0．05）。本次随访结果表明,虽然国产酵母疫苗免后5年的抗体阳转率和抗体GMT与剂量相同的进口酵母疫苗的水平相当,但抗体阳转率已降至70％以下,应考虑加强接种。     

转基因细胞分泌乙型肝炎重组疫苗在儿童中的免疫原性初步研究

本文报告用转基因细胞B43分泌的乙型肝炎病毒表面抗原主蛋白经纯化制成的87-4批重组疫苗进行临床接种观察的结果,同时用8723-1批血源疫苗作对照。疫苗接种采用0、1、2月各接种1针的方案。重组疫苗共接种111名8～13岁儿童,分为20μg、10μg及5μg 3组,血源疫苗分为20μg、10μg 2组。所有儿童接种前检查乙型肝炎病毒表面抗原、抗体及核心抗体均阴性.20μg组1针后1个月,重组疫苗阳转率60.5％,血源疫苗为31％;2针后1个月,两种疫苗的阳转率分别为100％和72.4％;血源疫苗3针后1个月阳转率也仅79.3％。3针后1个月两种疫苗的抗体几何平均滴度(GMT)分别为492.7和207.4mIU。但重组疫苗6个月后血清抗体的GMT为628mIU。10μg组1针后1个月的阳转率重组疫苗为21.7％,血源疫苗为20.9％;2针后1个月分别为87％及62.8％;3针后1个月分别为100％及81.4％。抗体GMT分别为163.7和129.6mIU.5μg组的重组疫苗免疫后6个月100％阳转,其GMT为56mIU。结论认为无论从阳转率或几何平均滴度分析判断,重组疫苗均优于血源疫苗。     

新生儿接种流感嗜血杆菌乙型肝炎偶联疫苗（COMVAX^TM）的安全性和免疫效果研究

将出生时接种过重组酵母乙肝疫苗的131名HBsAg阴性母亲的新生儿,随机分为两组,一组接种COMVAX^TM,另一组接种单价乙肝疫苗和单价流感嗜血杆菌偶联疫苗,出生时第一针乙肝疫苗接种后,应用2,4,13月程序免疫,在2,4月免疫后,接种COMVAX^TM组和对照组新生儿中无一例发生重度副反应,接种COMVAX^TM组新生第一针免疫前（2月）和二针免后一个月（5月）的抗－HBs阳转率分别为53．73％和95．00％,抗全GMT分别为104．10和56．29,均与接种单价组无显著差异,第二针免疫后一个月接种COMVAX^TM组96．00％新生儿抗－PRP抗体达到长期保护临界值（1.0ug/ml)水平,而接种单价流感嗜血杆菌疫苗组新生儿为95．20％,结果表明,对于健康母亲所生的新生儿,接种COMVAX^TM疫苗,抗－HBs和抗－PRP抗体阳转率及滴度均不低于接种单价疫苗组。     

Immunogenicity and adverse reactions of influenza vaccination in elderly patients given acetaminophen or placebo

The objective was to examine the antibody responses to influenza immunization in an elderly population and the effect of prophylactic acetaminophen on adverse responses due to inactivated whole virus vaccine containing influenza A (H3N2 and H1N1) and B antigens. During the autumn of 1990, 100 patients 65 years or older were immunized and randomly allocated to receive placebo or 1,950 mg (2 x 975 mg) of acetaminophen. They recorded any local and systemic side effects over a 3-day period. Serology was performed on pre- and post (4-6 weeks) -vaccination sera. Age and gender distribution in the study were: 47% who were 75 years or older, and 61% of the patients were female. Most of the patients (97%) had pre-existing antibodies to Influenza A or B. Average peak preimmunization antibody titers were 40 to B Yamagata and A Taiwan (H1N1) and 80 for A Shanghai (H3N2). Half of each treatment group had a 4-fold or greater rise in antibody titer in response to the vaccine. Only 30% of patients immunized the previous year but 80% of those never vaccinated previously demonstrated a 4-fold or greater serological response to the vaccine. However, measurement of protection rates (HI >/= 40) before and after vaccination indicated 81.1-100% protection for the 3 viruses not influenced by treatment, gender or a history of previous vaccination. Both treatment groups had equally small numbers of patients who recorded systemic symptoms of drowsiness, myalgia, fever and chills and about 50% had arm soreness. Although about 80% of previously unimmunized adults mounted a 4-fold antibody rise to influenza vaccine antigens whereas booster effects were seen in only 30% of those immunized the previous year, protection rates were high (81-100%) after immunization and were not affected by acetaminophen treatment. Adverse effects (15% systemic and 50% local) were not ameliorated by 1950 mg of acetaminophen in these elderly patients.     

Immunogenicity and Safety in Adults of a New Chromatographically Purified Vero-cell Rabies Vaccine (CPRV): a Randomized, Double-blind Trial with Purified Vero-cell Rabies Vaccine (PVRV)

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.     

Expression of a recombinant chimeric protein of hepatitis A virus VP1-Fc using a replicating vector based on Beet curly top virus in tobacco leaves and its immunogenicity in mice

We describe the expression and immunogenicity of a recombinant chimeric protein (HAV VP1-Fc) consisting of human hepatitis A virus VP1 and an Fc antibody fragment using a replicating vector based on Beet curly top virus (BCTV) in Agrobacterium-infiltrated Nicotiana benthamiana leaves. Recombinant HAV VP1-Fc was expressed with a molecular mass of approximately 68?kDa. Recombinant HAV VP1-Fc, purified using Protein A Sepharose affinity chromatography, elicited production of specific IgG antibodies in the serum after intraperitoneal immunization. Following vaccination with recombinant HAV VP1-Fc protein, expressions of IFN-γ and IL-4 were increased in splenocytes at the time of sacrifice. Recombinant VP1-Fc from infiltrated tobacco plants can be used as an effective experimental immunogen for research into vaccine development.     

国产腮腺炎和进口麻风腮疫苗免后腮腺炎HI抗体比较

报道了用国产流行腮腺炎减毒活疫苗和美国产麻－风－腮减毒活疫苗接种８～９岁小学生后,采血进行ＨＩ抗体测定比较,其抗体阳转率均在８０％左右,ＧＭＴ为７．３５～１０．０３,说明两种疫苗均有较好的免疫应答     

冻干A+C群脑膜炎球菌多糖疫苗安全性和免疫原性观察

为了评价冻干A+C群脑膜炎球菌多糖疫苗(MPV)的安全性和免疫原性,按随机、盲法的原则,评价疫苗免疫后不良反应发生率、抗体阳转率及抗体几何平均滴度(GMT)。将606名健康观察者分为2～5岁、6～12岁、13～17岁、18～60岁四个年龄组,结果显示,该疫苗全身反应发生率2.64%,局部反应发生率1.32%,四个年龄组疫苗免疫后杀菌抗体阳性率分别为100%、100%、99.3%和100%,免疫后A群杀菌抗体GMT分别为1:250.47、1:190.61、1:144.22和1:205.79,免疫后C群杀菌抗体GMT分别为1:273.33、1:551.18、1:788.26和1:809.81,冻干A+C群多糖疫苗在≥2岁人群中具有良好的安全性和免疫原性,建议推广使用A+C群MPV。     

Evaluation of inactivated hepatitis A vaccine in Canadians 40 years of age or more.

OBJECTIVE: To assess the side effects and immune responses after three serial doses of a new inactivated hepatitis A vaccine in people 40 years of age or more. DESIGN: Open, noncomparative trial. SETTING: A hospital, a regional laboratory and public health units in British Columbia. PARTICIPANTS: A volunteer sample of 64 healthy adults aged 40 to 61 years who were seronegative for hepatitis A virus (HAV). All were staff or associates of the health facilities. Exclusion criteria included elevated serum alanine and aspartate aminotransferase levels, a history of liver disease and recent travel to areas of high risk for HAV infection. INTERVENTION: A formalin-inactivated, alum-adsorbed vaccine containing 720 ELISA (enzyme-linked immunosorbent assay) units of antigen from HAV strain HM175 per 1.0-mL dose was injected intramuscularly into the delgoid area. The second and third doses were given 1 and 6 months later respectively. MAIN OUTCOME MEASURES: A detailed diary of any adverse effects for 3 days after each dose. HAV antibody levels in blood samples taken before and 30 days after each dose. RESULTS: All subjects completed the planned series of vaccinations and blood tests; symptom diaries were returned after 190 (99%) of 192 vaccinations. Local symptoms, most often soreness, were reported after 46% of the vaccinations but were mild and usually resolved within 24 hours. A temperature of more than 38.0 degrees C was never reported. Seroconversion occurred in all cases after the two primary doses, and the subjects were still seropositive at 6 months. After the booster dose the geometric mean titre was 2380 mIU/mL, all values being 200 mIU/mL or greater. CONCLUSION: In healthy adults 40 years of age or more the HAV vaccine was well tolerated and highly immunogenic. Final antibody levels were much higher than reported in people passively immunized against HAV with immune serum globulin.     

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province,China: Increased Susceptibility in Adults

BackgroundHepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program.ObjectiveTo understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades.MethodsThis study used the 2005–2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province.ResultsThe overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001). During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001). Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases.ConclusionsChildhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.     

风疹减毒活疫苗主种子批毒种(松叶株)的安全性和免疫原性检测

评价兰州生物制品研究所用风疹病毒松叶株主种子批毒种制备的冻干风疹减毒活疫苗的安全性和免疫原性。采用自身对照、开放性的免疫原性临床观察试验,对100名8～10月龄筛选后符合条件的健康易感儿童,皮下接种1剂风疹减毒活疫苗,观察其免疫后的局部和全身反应并采集每个受试者免前和免后35d的血清标本,检测风疹HI抗体,计算阳转率和几何平均滴度。试验中所有受试者在系统观察期内均未观察到注射部位局部的不良反应;总的发热率为5%,且均为轻度发热;有1例在观察期内出现腹泻和咳嗽并持续5d,发生率为1%,属中度全身反应;血清风疹病毒抗体(HI)阳转率为100%,GMT为1:638.7±1.7。该疫苗与国内、外其它种类的风疹疫苗一样具有良好的安全性和免疫原性。     

大连市15岁以下儿童流行性腮腺炎感染状况及其疫苗免疫效果观察

为了解儿童中流行性腮腺炎(腮腺炎)的免疫情况,观察腮腺炎减毒活疫苗的安全性和免疫原性。选取353名1~15岁儿童进行血清流行病学调查;对157名城、乡3~5岁儿童进行疫苗效果观察,并将其随机分成实验组和对照组;采用酶联免疫吸附试验(ELISA)检测血清IgG。接种疫苗24h、48h、72h、96h后观察人体不良副反应;并分别在接种前及接种后1个月,分别采集免疫对象静脉血测定抗体。353名1~15岁儿童中腮腺炎抗体阳性179人,总阳性率为50.71%;0~1岁、2~6岁、7~12岁和13~15岁4组的抗体阳性率分别为21.84%、36.17%、69.41%和77.01%。实验组44名抗体阴性儿童接种了腮腺炎减毒活疫苗,1个月后抗体阳转率为93.18%,IgG呈4倍增长者23人,4倍增长率为52.27%。无一例出现严重的不良副反应。     

Assessing immune competence in pigs by immunization with tetanus toxoid

Immune competence can be tested by challenging organisms with a set of infectious agents. However, disease control requirements impose restrictions on the infliction of infections upon domestic pigs. Alternatively, vaccinations induce detectable immune responses that reflect immune competence. Here, we tested this approach with tetanus toxoid (TT) in young domestic pigs. To optimize the vaccination protocol, we immunized the pigs with a commercial TT vaccine at the age of 21 or 35 days. Booster immunizations were performed either 14 or 21 days later. TT-specific antibodies in plasma as well as lymphoproliferative responses were determined both 7 and 14 days after booster immunization using ELISA and lymphocyte transformation tests, respectively. In addition, general IgG and IgM plasma concentrations and mitogen-induced proliferation were measured. The highest TT-specific antibody responses were detected when blood samples were collected 1 week after a booster immunization conducted 21 days after primary immunization. The pigs’ age at primary immunization did not have a significant influence on TT-specific antibody responses. Similarly, the TT-specific proliferative responses were highest when blood samples were collected 1 week after booster immunization, while age and time of primary and booster immunization were irrelevant in our setup. While general IgG and IgM plasma levels were highly age dependent, there were no significant age effects for TT-specific immune responses. In addition, mitogen-induced proliferation was independent of immunization as well as blood sampling protocols. In summary, our model of TT vaccination provides an interesting approach for the assessment of immune competence in young pigs. The detected vaccination effects were not biased by age, even though our data were acquired from immune systems that were under development during our tests.