肾综合征出血热I型疫苗中期流行病学效果研究

目的：观察肾综合征出血热I型灭活疫苗在浙江省肾综合征出血热高发疫区大面积人群接种后的安全性,考核流行病学防病效果。方法 采用IFAT法测特异性IgG抗体,用MCPENT法测中和抗体滴度。结果 共接种10460人,全程接种者占97.30%,对照16159人。全程接种后2周荧光抗体阳转率为100.00%(67/67),中和抗体阳转率为44.44%,几何平均滴度分别为72.14%和4.63。加强免疫后血清抗体迅速回升,1年后又逐渐下降。预防接种后全身反应和局部反应轻微。接种组无发病,对照组发病24例,死亡3例。疫苗中期（基础免疫后4年）流行病学防病效果良好,人群保护率达100%（95%可信区间为96.3%～100%）。结论 HFRS疫苗安全性良好,中期流行病学防病效果明显,取得了良好的经济和社会效益。     

流行性乙型脑炎减毒活疫苗人体接种反应及免疫持久性观察研究

为了进一步了解流行性乙型脑炎减毒活疫苗的接种安全性，掌握其免疫效果及免疫持久性，本研究有代表性地抽取2岁以内婴幼儿359名，并将其分为两组，分别接种乙脑灭活疫苗和动脑减毒活疫苗。经现场观察证实，两种疫苗接种后，仅极个别出现轻度接种反应，无严重反应发生，因而两种疫苗均是安全的。采用前瞻性方法研究其免疫学效果发现，基础免疫后，两种疫苗所产生的血清抗体达60％左右，但仅能维持1年，第2年需加强免疫，之后，抗体阳性率迅速提高至90％以上，减毒活疫苗高于灭活疫苗，抗体平均滴度也大为提高。经过2～3年的间隔期减毒活疫苗的抗体阳性率尚维持在80％和70％，而灭疫苗已下降在近50％和35％，提示减毒活疫苗具有更好的免疫学效果、更少的接种次数和接种剂量，适宜于大面积推广应用。根据观察结果，我们认为，乙脑灭活疫苗免疫，应基础免疫2针，间隔7～10天，第2年加强免疫1针之后，间隔1年最迟2年再加强1针。减毒活疫苗基础免疫1针，第2年加强1针，经4～5年后再加强注射。     

动物致伤人群接种狂犬病疫苗后血清学与流行病学效果的初步分析

目的观察就诊的动物致伤者,分别全程足量接种两种剂型狂犬病疫苗后,其血清中抗体阳转率和疫苗保护率。方法2000—2001年就诊者全程接种浓缩苗,2002—2003年的全程接种精制纯化(vero细胞)苗。严重致伤者,于0、3天接种加倍量疫苗,并于0天的同时,对其伤口周围用抗狂犬病血清(40IU/kg)进行浸润注射。联合使用抗血清者,完成全程5次注射后第15、75天各加强1针疫苗。接种结束后15—20天,以间接混合酶标法检测血清中抗狂犬病病毒抗体。期内经疫情报告系统,收集当年观察人群狂犬病病例,计算两接种组人群的发病率,并分别与当年未接种疫苗的动物致伤人群比较,以估算疫苗保护率。结果4年中该人群抗体总阳性率为95.60%。接种精制纯化苗组的阳性率为96.37%,高于浓缩苗组的94.83%。狂犬病疫苗保护率,精制苗1年和2年的均为100.00%;浓缩苗1年的为95.46%,2年、3年和4年的为90.91%。结论动物致伤人群规范处理局部伤口后,及时全程接种狂犬病疫苗,其抗体阳性率较高。国产精制纯化苗接种人群的抗体阳性率和1~2年的疫苗保护率高于浓缩苗。从我国狂犬病防治工作实际出发,提示国产精制纯化苗需尽快降低成本,以巩固和提高其接种率。     

人用狂犬病纯化疫苗(Vero细胞)临床观察及免疫学效果研究

目的　研究人用狂犬病纯化疫苗的安全性和保护性。方法　采用狂犬病疫苗暴露后免疫程序接种受试人群 ,I期临床接种 2 0人 ,II、III期临床接种 30 4人 ,观察注射后反应 ,采用小鼠脑内中和试验法测定其中 6 2人中和抗体水平。结果　全部受试者有 13.2 7%出现轻度副反应 ,无中强度副反应 ,中和抗体阳转率为 10 0 % ,中和抗体GMT为 11.89IU/ml。结论　该疫苗对人体安全且具有较好的免疫原性     

双价肾综合征出血热纯化疫苗免疫效果观察

目的观察双价肾综合征出血热(HFRS)纯化疫苗的免疫效果。方法按0、14d2针基础免疫和6个月后1针加强免疫的程序对适龄人群接种双价HFRS纯化疫苗,采用队列研究方法,对接种组和对照组连续观察3年并进行比较分析。结果 3年观察期内疫苗接种组HFRS发病密度为0,对照组发病密度为6.51/10万,差异有统计学意义(χ2=21.77,P<0.01),疫苗接种3年内保护率达100%。结论双价HFRS纯化疫苗按照0、14d2针基础免疫和6个月后1针加强免疫程序接种,免疫效果良好。     

日本脑炎病毒DNA疫苗和基因工程亚单位颗粒疫苗的动物保护实验研究

目的　评价 3种日本脑炎病毒 (JEV)新型疫苗 ,即E蛋白病毒样颗粒 (VLPs)、DNA疫苗 (pV/JE)以及E蛋白颗粒 (Eps)的动物免疫效果。方法　BALB/c小鼠经 2次接种疫苗后 ,测定其病毒特异性的CTL活性、结合抗体、中和抗体 ,并以10LD5 0JEV攻击免疫小鼠 ,观察其保护效果。结果　各新型疫苗组的CTL活性为 33%～ 5 6 % ,灭活疫苗组为 2 2 % ,而载体和PBS对照组的CTL活性分别为 17%和 18%。一次免疫后 ,实验组小鼠血清结合抗体阳转率为 90 %。除DNA疫苗组外 ,各组小鼠的二次免疫血清抗体效价高于一次免疫的抗体效价 (P <0 0 5 ) ,且以VLPs加佐剂组小鼠血清抗体效价最高 ,Eps加佐剂组次之 ,均高于 pV/JE组和灭活疫苗组 (P <0 0 5 )。三种疫苗可诱发小鼠产生中和抗体。各实验组小鼠能够抵抗JEV的攻击 ,而对照组小鼠的死亡率为 37 5 %。结论　三种新型疫苗可以正确表达JEV的E蛋白表位 ,可诱发免疫小鼠产生抗JEV的中和抗体并有保护性作用 ,免疫效果优于灭活疫苗 ,有可能成为候选的JEV新型疫苗。     

汉坦病毒包膜糖蛋白G1、G2基因的DNA免疫

目的　将编码汉坦病毒浙 37(Z37)株包膜糖蛋白G1、G2的真核表达质粒免疫小鼠 ,观察其能否诱导体液免疫应答。方法　重组质粒 pcDNA3.1 G1、pcDNA3.1 G2以不同方式免疫BALB/C小鼠 ,用免疫荧光测定 (IFA)法检测血特异性抗体 ,用半微量直接免疫酶斑减少中和试验检测血中和抗体。经肌内注射途径免疫 15只BALB/C小鼠 ,3组小鼠分别注射 10 0 μgpcDNA3.1、pcDNA3.1 G1、pcDNA3.1 G2 ;每只小鼠免疫 3次 ,初次免疫后 4周 ,加强 2次 ,间隔 3周。经基因枪免疫 9只BALB/C小鼠 ,3组小鼠分别注射 1.5 μgpcDNA3.1、pcDNA3.1 G1、pcDNA3.1 G2 ;每只小鼠免疫 2次 ,初次免疫后 4周 ,加强 1次。结果　 1.经肌内注射免疫时 ,产生特异性抗体的小鼠个数分别是 :pcDNA3.1 G1组为 5只中 3只 ,pcDNA3.1 G2组为 5只中 2只 ;荧光抗体滴度 1∶2 0～ 1∶80 ;产生中和抗体的小鼠个数分别是 :pcDNA3.1 G1组为 5只中 1只 ,pcDNA3.1 G2组为 5只中 2只 ;中和抗体滴度 1∶10～ 1∶2 0。 2 .经基因枪免疫时 ,实验组小鼠都产生了特异性抗体和中和抗体。荧光抗体滴度 1∶2 0～ 1∶32 0 ,中和抗体滴度≥ 1∶10。结论　重组质粒 pcDNA3.1 G1、pcDNA3.1 G2能诱导小鼠产生有效的体液免疫应答     

673名健康志愿者乙肝疫苗免疫接种效果及影响因素分析

目的观察济宁地区普通人群20μg重组乙型肝炎疫苗(CHO细胞)免疫接种后抗-HBs转阳率,探讨疫苗免疫接种者抗-HBs转阳率的影响因素。方法 673名健康志愿者,分别于0、1、6月各接种20μg重组乙型肝炎疫苗。全程免疫后1～2个月采血,分离血清,采用ELISA法检测抗-HBs抗体,评价免疫效果,并分析年龄和性别对血清抗-HBs抗体转阳的影响。结果 673名健康志愿者接种20μg重组乙型肝炎疫苗(CHO细胞)后血清抗-HBs抗体阳性率为92.57%,不同年龄组抗体阳性率差异有统计学意义(P<0.001),男女抗-HBs抗体阳性率差异有统计学意义(P<0.001)。结论 20μg重组乙型肝炎疫苗(CHO细胞)免疫接种后血清抗-Hbs抗体阳性率较高。年龄、性别均可影响免疫接种后抗-HBs抗体转阳率。     

HFRSⅡ型疫苗4年血清学效果追踪观察

肾综合征出血热 型 (HFRS— 型 )灭活疫苗在大范围人群流行病学观察显示安全性较好 ,并且有良好的血清学效果〔1〕。本文追踪观察该苗 4年来抗体消长情况。现将结果报告如下 :1　材料与方法1.1　疫苗由长春生物制品研究所生产 HFRS地鼠肾细胞灭活疫苗。基础免疫疫苗批号为 940 90 3— 2、940 90 3— 3,加强免疫疫苗批号为 95 0 70 4— 9均在有效期内使用。1.2　免疫程序和采血时间　按照 0、2 8、42天免疫程序进行基免接种 ,1年后加免 1针 ,并分别于基免前、基免全程后 15天、1年、加免后 15天及加免后 2年、3年采集静脉血分离血清进…     

布鲁氏菌病M5、S2疫苗免疫血清半抗原-琼脂扩散试验方法检测评价

目的 应用NH-AGID方法对布鲁氏菌M5、S2疫苗株免疫血清进行检测，评价该方法适用性。方法 选取3～5月龄羔羊74只，随机分为3组。分别以S2株1.0×10¹⁰ CFU、5.0×10⁹ CFU灌服和皮下注射接种羔羊各25只，M5株以1.0×10⁹ CFU皮下注射接种羔羊24只。免疫后7 d～150 d采集羊全血，分离血清，经RBT初筛和SAT确诊免疫抗体阳性血清。评估NH-AGID方法对M5和S2株疫苗免疫抗体与感染抗体的鉴别诊断特异性。结果 NH-AGID方法对M5株疫苗免疫阳性血清的LPS抗体检出率为100%,NH抗体检出率8.3%～29.2%,鉴别诊断特异性为82.8%。对S2株疫苗口服组免疫阳性血清的LPS抗体检出率为31.2%～66.7%,NH抗体检出率为0%;皮下注射组免疫阳性血清的LPS抗体检出率为45.4%～100%,NH抗体检出率为4.5%～20%。对S2株疫苗免疫血清的鉴别诊断特异性为96.5%。结论 NH-AGID方法不完全适用于羊用布鲁氏菌疫苗M5株和S2株的鉴别诊断，该方法的鉴别诊断特异性与...     

不同效价出血热灭活疫苗人体接种后的中和抗体应答及其对两个型汉坦病毒的交叉反应

以不同效价的出血热疫苗免疫人体后,４ 批效价合格的疫苗中和抗体阳转率达８７ ％ ～１００％ ,抗体ＧＭＴ达１５ ～１８,而一批未达合格标准的疫苗阳转率只有６０ ％ ,ＧＭＴ７－１ ;免疫血清对同型毒株的抗体阳转率为１００％ ,对异型只为２５ ％ 。为保证疫苗在人体应用的有效性,应研究及制备ＨＴＮ和ＳＥＯ两型的双价疫苗。     

Phase I safety and immunogenicity study of a Brazilian serogroup B vaccine

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18–44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 μg, 25 μg and 50 μg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.     

肾综合征出血热灭活疫苗免疫大鼠的抗体应答

本文对实验大鼠进行单价肾综合征出血热灭活疫苗免疫，结果表明免疫大鼠能产生较高的同型和异型中和抗体及IFA抗体应答，因而，大鼠可以作为疫苗效力评价的实验动物。     

IgG subclass distribution of hepatitis B surface antigen antibodies induced in children with chronic hepatitis B infection after interferon-alpha therapy

The IgG subclass distribution of antibody to hepatitis B surface antigen (anti-HBs) was investigated in 19 children with chronic active hepatitis B infection who showed a complete serological seroconversion after interferon-alpha therapy. Determinations were done 6 and 12 months after treatment. Our results showed no selectivity in anti-HBs synthesis among IgG subclasses. All 4 IgG isotypes were involved in the response, with similar percentage contributions, on average, of IgG1 (35%), IgG3 (27%), and IgG4 (28%), followed by IgG2 (10%). IgG4 became the second most dominant isotype at the end of observation. These results are in contrast to those found after natural seroconversion, in which anti-HBs was highly restricted to neutralizing IgG1 and IgG3, with only a minor contribution from IgG2 and IgG4. It is postulated that analysis of the specific profiles of IgG subclasses may be of value for the estimation of the therapeutic efficacy of recombinant interferon-alpha used and may be helpful in choosing more-effective treatment.     

Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration,ratio, and multiple doses

Dengue fever, caused by four serotypes of a mosquito-borne virus, is a growing problem in tropical countries. Currently, there is no treatment or vaccine. We evaluated safety and immunogenicity of two doses, given six months apart, of seven formulations of dengue tetravalent live-attenuated vaccine (containing different concentrations of the component viruses) versus placebo in 59 flavivirus-seronegative Thai adults. The first dose was the more reactogenic. Most volunteers experienced clinically moderate fever, headache, myalgia, eye pain or rash 7-11 days after injection, generally lasting three days or less. Modest decreases in platelets and neutrophils were observed. After one dose, 58% of dengue recipients seroconverted (neutralizing antibody level > or = 1:10) against > or = 3 serotypes; 35% seroconverted against all four. After the second dose, seroconversion was 76% and 71%, respectively. All subjects seroconverted to serotype 3 after one dose. Serotype 4 elicited the lowest primary response but the highest increase in seroconversion after the second dose.     

Immunogenicity of measles and rubella vaccines in Oman: a prospective clinical trial

A prospective immunogenicity trial of measles and rubella vaccines was conducted in Oman. Children received measles vaccine at age 9 months and measles-rubella vaccine at age 15 months. Serum specimens were tested for measles-specific IgG and rubella-specific IgG. Of 1025 eligible infants, 881 (86.0%) returned for all five visits and had adequate serum samples for testing. Seroconversion to measles after vaccination at 9 months was 98.1%. At 15 months, 47 (5.3%) of the 881 children were seronegative for measles; of these, 44 (93.6%) seroconverted. At 16 months, 99% of the children seronegative at age 9 months seroconverted after receiving two doses of measles vaccine. At age 15 months, 684 (77.6%) children were seronegative for rubella. Of these, 676 (98.8%) seroconverted by age 16 months. One dose of measles vaccine at age 9 months was highly immunogenic. One dose of measles-rubella vaccine at age 15 months closed the remaining measles immunogenicity gap and resulted in a high rate of rubella seroconversion.     

MM-7基因工程双价疫苗对新疆细毛羊免疫效果的研究

应用ＭＭ－７基因工程双价疫苗免疫产前１５天的新疆细毛孕母羊，并通过改变产前１５天孕母羊机体免疫水平，由初乳被动免疫羔羊。在免疫孕母羊后１０，２０，３０，４０，５０，６０，７０天分别检测免疫组及对照组血清特异性中和抗体ＩｇＧ及ＩｇＡ动态水平，观察两组腹泻发病率，死亡率情况和ＭＭ－Ｕ基因工程双价疫苗的免疫保护效果。     

Primary vaccine failure after 1 dose of varicella vaccine in healthy children

Universal immunization of young children with 1 dose of varicella vaccine was recommended in the United States in 1995, and it has significantly decreased the incidence of chickenpox. Outbreaks of varicella, however, are reported among vaccinated children. Although vaccine effectiveness has usually been 85%, rates as low as 44% have been observed. Whether this is from primary or secondary vaccine failure-or both-is unclear. We tested serum samples from 148 healthy children immunized against varicella in New York, Tennessee, and California to determine their seroconversion rates, before and after 1 dose of Merck/Oka varicella vaccine. The median age at vaccination was 12.5 months; postvaccination serum samples were obtained on average 4 months later. Serum was tested for antibodies against varicella-zoster virus (VZV) by use of the previously validated sensitive and specific fluorescent antibody to membrane antigen (FAMA) assay. Of 148 healthy child vaccinees, 113 (76%) seroconverted, and 24% had no detectable VZV FAMA antibodies. Our data contrast with reported seroconversion rates of 86%-96% by other VZV antibody tests and suggest that many cases of varicella in immunized children are due to primary vaccine failure. A second dose of varicella vaccine is expected to increase seroconversion rates and vaccine effectiveness.     

Mucosal HIV-binding antibody and neutralizing activity in high-risk HIV-uninfected female participants in a trial of HIV-vaccine efficacy

BACKGROUND: This study investigated gp120-binding antibody and neutralizing activity, at the gingival- and cervical-mucosal levels, in response to a bivalent gp120 candidate vaccine. METHODS: Women who met the study's inclusion criteria for documented high-risk behaviors participated in a nested substudy of the multicenter phase 3 trial of human immunodeficiency virus (HIV)-vaccine efficacy, VAX004. Gingival, cervicovaginal lavage, and plasma specimens were collected at 6-month intervals for 3 years. Binding-antibody and neutralizing-activity assays quantified the presence of anti-HIV activity in mucosal specimens. RESULTS: Vaccine recipients were more likely than placebo recipients to have IgG binding antibodies in all 3 compartments tested and to have only IgA binding antibody in plasma (P<.0001). The relationship between vaccine and cervicovaginal IgG achieved significance (odds ratio [OR], 6.6 [P=.01]) but was weakened by the presence of cervicovaginal leukocytes. There was no relationship between immunization and the presence of neutralizing activity, in either bivariate or multivariate modeling (OR, 6.0 [P=.29]).CONCLUSIONS: Vaccination is associated with the presence of both gp120-binding IgG in all compartments and plasma IgA but not with neutralizing activity. There is a role for the measurement of mucosal immunity in response to candidate vaccines and, in particular, for a determination of HIV-specific neutralizing antibodies.     

福建省新丙五价钩端螺旋体菌苗接种后反应与免疫效果的观察

目的对观察对象接种“福建新丙五价”钩体菌体苗基础免疫和一年后加强免疫的反应及效果进行观察。方法观察记录各针次疫苗接种后的反应并采集观察对象免疫前及免疫后20d,90d,180d,360d及再加强免疫后20d的6份血清,用显微镜凝集试验(MAT)测定各群抗体滴度,以抗体滴度≥1∶10为阳性判别标准,计算疫苗接种前后各次各群抗体阳转率和几何平均滴度GMT。结果观察对象均未出现全身反应,局部反应以复种为多,女性复种后反应比男性更严重,差异具有显著性意义。免疫后血清抗体阳转率及几何平均滴度(GMT)均比免疫前有显著的增长,且在免疫后3个月阳转率达高峰为95%以上,一年后维持50%左右,几何平均滴度(GMT)在基础免疫后1个月为1∶:60左右,半年后降为1∶20,一年后为1∶10。再次强化免疫,抗体阳转率迅速上升,高达100%,几何平均滴度(GMT)上升到1∶100。结论“福建新丙五价”钩体菌体苗的安全性及免疫效果是肯定的,只要加强钩体病的监测,菌苗的菌型与当地流行菌群吻合并按照规定程序免疫接种,完全可以预防钩体病的流行。