无针皮内免疫接种Sabin IPV疫苗的安全性及免疫原性研究

全球消灭脊髓灰质炎野病毒后,必须全面使用脊髓灰质炎灭活疫苗(Inactivated poliovirus vaccine,IPV)才能维持无脊灰状态,然而IPV成本较高,难以满足全球需要。皮内免疫途径能够降低Sabin株脊髓灰质炎灭活疫苗(Vero细胞)(Inactivated poliovirus vaccine derived from Sabin strains,sIPV)的抗原量,本研究将评估无针皮内免疫sIPV的安全性及免疫原性。本研究采用中国医学科学院医学生物学研究所生产的sIPV进行1/5(0.1 ml)剂量无针皮内免疫接种Wistar大鼠,并设计全剂量肌肉免疫对照组以及无针皮内免疫阴性对照组,按0月、1月、2月基础免疫程序,于免疫前及每剂免疫后第30 d釆血,检测血清中和抗体水平,评价免疫原性,并通过观察大鼠的皮肤刺激反应及豚鼠的全身过敏反应,评价安全性。Wistar大鼠3剂免疫后,1/5剂量皮内免疫组与全剂量肌肉免疫组Ⅰ、Ⅱ、Ⅲ型抗体阳转率均达到100%,各型别中和抗体几何平均滴度(Geometric mean titer,GMT)均远高于1∶8保护水平。大白鼠接种疫苗后体重增加,皮肤刺激试验及全身过敏反应试验结果表明无针皮内免疫sIPV具有良好的安全性。本研究结果表明sIPV疫苗无针皮内注射免疫安全、有效,并可降低sIPV的抗原量,可为全球消灭脊髓灰质炎提供可负担得起的疫苗。     

婴儿脊灰母传抗体对Sabin株脊髓灰质炎灭活疫苗不同序贯免疫接种程序效果的影响

目的探讨婴儿脊髓灰质炎(简称脊灰)母传抗体对Sabin株脊髓灰质炎灭活疫苗(Sabin inactivated poliovirus vaccine,s IPV)与不同剂型脊髓灰质炎减毒活疫苗(oral poliovirus vaccine,OPV)采用不同序贯免疫程序接种效果的影响。方法选取柳州市600名2月龄无脊髓灰质炎疫苗免疫史的常住健康婴儿,分为6个序贯免疫组,其中1剂s IPV+2剂b OPV 2组:s IPV+2b OPV(糖丸)组、s IPV+2b OPV(液体)组;2剂s IPV+1剂b OPV 2组:2s IPV+b OPV(糖丸)组、2s IPV+b OPV(液体)组;2剂s IPV+1剂t OPV 2组:2s IPV+t OPV(糖丸)组,2s IPV+t OPV(液体)组。每组100人。按照0、28、56 d程序,分别在婴儿2、3、4月龄时接种相应疫苗。检测免前、全程免后28 d血清中脊灰中和抗体滴度,计算阳转率及GMT。结果 6个序贯免疫组免前各项指标分布均匀,各型脊灰抗体阳性率、抗体水平及分布均无明显差异。共有518例免前和免后配对血清抗体检测结果的研究对象进入免疫原性分析。s IPV+2b OPV组与2s IPV+b OPV组Ⅱ型抗体、2s IPV+t OPV(糖丸)组Ⅲ型抗体免前阴性和免前阳性者接种疫苗后阳转率差异均有统计学意义;s IPV+2b OPV(糖丸)组Ⅲ型抗体,2s IPV+b OPV(糖丸)组与2s IPV+b OPV(液体)组Ⅱ型抗体,2s IPV+t OPV(糖丸)组Ⅰ、Ⅱ型抗体的免前阳性与免前阴性者接种疫苗后的GMT差异均有统计学意义;2s IPV+t OPV(糖丸)Ⅰ型抗体组与2s IPV+t OPV(液体)Ⅱ型抗体组中,免前8~32、≥32两种滴度水平的免后GMT差异均有统计学意义。结论脊灰疫苗序贯免疫效果受脊灰母传抗体干扰。     

森林脑炎灭活疫苗加强免疫效果及免疫持久性观察

目的评价森林脑炎灭活疫苗加强免疫效果以及免疫持久性。方法采用单中心无对照设计,在吉林省选择571名≥8岁受试者进行疫苗基础免疫,其中400名受试者进行加强免疫,加强免疫后选择54名进行免疫持久性研究。于基础免疫前及免疫后1、6和12个月分别采血,加强免疫前及免疫后1、6、12、18、24、30、36和42个月分别采血检测抗体浓度,计算抗体阳性率和抗体几何平均浓度(geometric mean concentration, GMC)。结果基础免疫后1、6和12个月,抗体阳性率分别为96.05%、86.45%、76.95%,GMC值分别为753、332和225 VIEU/mL。加强免疫后1、6和12个月,抗体阳性率分别为95.87%、94.33%、91.54%,GMC值分别为3 391、2 322和1 981 VIEU/mL。加强免疫后42个月GMC值为747 VIEU/mL。结论森林脑炎疫苗加强免疫后具有良好的免疫持久性,与基础免疫相比,加强免疫具有更好的免疫应答。     

Sabin IPV疫苗在版纳小耳猪体内的免疫原性及安全性研究

目的评价Sabin株脊髓灰质炎灭活疫苗(inactivated poliovirus vaccine derived from Sabin strain,s IPV)在版纳小耳猪体内的免疫原性及安全性,为新型动物模型提供实验依据。方法采用中国医学科学院医学生物学研究所已经上市的s IPV疫苗,设计s IPV肌肉免疫实验组与野毒株IPV(IPV derived from wild strain,w IPV)肌肉免疫对照组,以及生理盐水阴性对照组,按0、1、2月基础免疫程序,接种版纳小耳猪,于免疫接种前及每剂免疫接种后第30天釆血,检测各组的血清中和抗体水平,评价免疫原性,并通过观察小耳猪的状态及体重情况,评价安全性。结果版纳小耳猪3剂免疫后,s IPV试验组与w IPV对照组Ⅰ、Ⅱ、Ⅲ型抗体阳转率均达到了100%,各型中和抗体几何平均滴度(GMT)均远高于1∶8保护水平。版纳小耳猪接种疫苗后体重增加,结果表明s IPV疫苗在版纳小耳猪动物模型中具有良好的安全性。结论 s IPV疫苗在版纳小耳猪体内具有良好的免疫原性及安全性,版纳小耳猪可作为评价s IPV疫苗的新型实验动物模型。     

中国婴儿中脊灰母传抗体水平对两种疫苗免疫效果的影响

为了了解2月龄婴儿中针对脊髓灰质炎病毒的中和抗体水平,并探讨母传抗体对脊髓灰质炎减毒活疫苗(OPV)和灭活疫苗(IPV)免疫效果的影响。对416名2月龄婴儿分别接种OPV和IPV,采集免疫前后血清,用微量中和法检测血清中Ⅰ、Ⅱ、Ⅲ型脊髓灰质炎病毒中和抗体滴度,评价抗体GMT水平及4倍增长情况。检测结果显示,2月龄婴儿母传抗体Ⅰ、Ⅱ、Ⅲ型阳性率分别为45%、38.2%和17.5%,抗体GMT水平为9.0、8.1和5.2。经接种两组疫苗后,母传抗体阳性者与阴性者免后抗体GMT水平相比,OPV组无明显差异,IPV组阳性者略低于阴性者。在免前抗体滴度<1∶32人群中,OPV组免后抗体滴度4倍增长率及几何滴度增长倍数分别为:Ⅰ型93.6%、71.2;Ⅱ型98.2%、43.7;Ⅲ型91.7%、47.9;IPV组免后抗体滴度4倍增长率及几何滴度增长倍数分别为:Ⅰ型82%、9.4;Ⅱ型62.8%、5.1;Ⅲ型95.6%、11.7;在免前抗体滴度1∶32～1∶128人群中,OPV组Ⅰ型92.3%、23;Ⅱ型86.4%、13.9;Ⅲ型55.6%、4.1;IPV组Ⅰ型48%、2.5;Ⅱ型15%、0.9;Ⅲ型55.6%、2.7。目前中国2月龄婴儿免前脊灰抗体阳性率较高,尤其是Ⅰ、Ⅱ型。脊灰母传抗体对两种疫苗免疫效果有一定干扰,对IPV疫苗的影响较为明显。     

狂犬病疫苗免疫效果观察的研究(一)

本试验通过改变现用疫苗的免疫程序及免疫方法,比较不同免疫程序的肌肉免疫和皮内减量免疫与常规免疫方法免疫后血清中和抗体水平,阳转率,免疫持久性等。试验结果表明,肌肉免疫法2-1-1及皮内减量法,即可减少疫苗用量,免疫效果亦优于常规法。     

国产b型流感嗜血杆菌结合疫苗免疫原性观察

目的:了解兰州生物制品研究所研制的b型流感嗜血杆菌结合疫苗的免疫原性。方法:采用单纯随机抽样方法对柳州市709名3～59月龄婴幼儿按照规定的免疫程序接种兰州所(或巴斯德)Hib疫苗,2年内在不同时段采集血清样本,采用ELISA方法检测Hib-PRP抗体滴度。结果:基础免疫后血清Hib-PRP抗体含量平均水平为18.043μg/ml,抗体阳转率为97.19%,1年后血清Hib-PRP抗体含量为7.575μg/ml,抗体阳转率为93.75%。加强免疫后血清Hib-PRP抗体含量为130.330μg/ml,抗体阳转率为100.00%,加强免疫1年后血清Hib-PRP抗体含量为51.723μg/ml,抗体阳转率为100.00%。基础免疫后接种巴斯德Hib疫苗组血清Hib抗体含量高于接种兰州所Hib疫苗组,抗体阳转率则没有差别;免后1年,接种兰州所Hib疫苗儿童体内Hib抗体含量平均水平高于接种法国巴斯德Hib疫苗儿童;其余各时段两组儿童血清Hib-PRP抗体含量及抗体阳转率均无差别。结论:兰州所Hib疫苗有较好的免疫原性和免疫持久性。     

肾综合征出血热(I型)纯化疫苗防病效果及免疫持久性观察

卫生部兰州生物制品研究所生产的肾综合征出血热（ＨＦＲＳ）（Ｉ型）纯化疫苗在陕西、湖南,浙江的出血热流行区进行了人群免疫效果观察。基础免疫三针后,中和抗体阳转率平均５０％,荧光抗体阳转率为８４２６％,全程接种者２６４９２人,疑似发病１人,保护率平均为９６％。对陕西长安县不同年龄的３０人进行了免疫后２５年抗体水平观察,中和抗体阳转率为５７％,有良好的免疫效果,并具有一定的免疫持久性。     

ELISA试剂盒检测Sabin株脊髓灰质炎灭活疫苗Vero细胞宿主蛋白残留量的验证

目的 验证ELISA试剂盒检测Sabin株脊髓灰质炎灭活疫苗(Sabin strain inactivated poliovirus vaccine, sIPV)中Vero细胞宿主细胞蛋白(host cell protein, HCP)残留量的适用性。方法 用同一批ELISA试剂盒检测sIPV中Vero细胞HCP残留量,验证其专属性、重复性、中间精密度、准确度、线性、范围、定量限和耐用性等指标。结果 将样品用2种不同稀释液(样品稀释液和疫苗稀释液)稀释后,检测Vero细胞HCP残留量结果均<12.5 ng/mL,表明该方法专属性强;同一检验人员检测同一样品6次,Vero细胞HCP残留量结果均<12.5 ng/mL;不同检验人员检测同一样品6次,Vero细胞HCP残留量结果均<12.5 ng/mL,表明具有良好的重复性和中间精密度;准确度试验中回收率均在99%～106%,CV为2%;在12.5～400.0 ng/mL的线性范围内,标准曲线线性良好(R²>0.98);定量限为50.0 ng/mL;显色时间在25～35 min内对实验无影响,显色...     

尼帕病毒融合蛋白和受体结合蛋白基因DNA免疫的研究

构建了表达哺乳动物密码子优化的NiV囊膜蛋白F和G基因的真核表达质粒pCAGG-NiV-F和pCAGG-NiV-G.细胞融合试验表明,重组NiV融合蛋白F和受体结合蛋白G在pCAGG-NiV-F、pCAGG-NiV-G共转染BHK细胞中获得表达,并具有良好生物学活性.真核表达质粒pCAGG-NiV-F、pCAGG-NiV-G和pCAGG-NiV-F pCAGG-NiV-G DNA分别按100μg/只的剂量肌肉注射免疫6周龄BALB/c小鼠,间隔4周加强免疫,第二次加强免疫3周后采血,分离血清备用.分别以重组杆状病毒感染Sf9细胞表达的重组NiV融合蛋白(rNF)和受体结合蛋白(rNG)为包被抗原,应用间接ELISA检测上述质粒DNA免疫血清中的特异性抗体,具有较高的敏感性和特异性.另外,中和试验结果表明,DNA免疫小鼠产生的特异抗体可有效中和NiV囊膜蛋白F和G介导的伪型VSV重组病毒侵入NiV易感宿主细胞的感染性,并且受体结合蛋白G基因DNA诱导中和抗体的滴度高于融合蛋白F基因DNA.结果表明,DNA疫苗具有防制尼帕病毒性脑炎的潜力.     

Immunogenicity and safety of Vi capsular polysaccharide typhoid vaccine in healthy persons in Korea

The purpose of this study was to evaluate the immunogenicity and safety of Salmonella Typhi Vi capsular polysaccharide vaccine (Vi vaccine) in Korea. The immunogenicity of a single dose of Vi vaccine was evaluated in 157 subjects (75 children and 82 adults) before and at 1, 6, and 12 months after vaccination. Immunogenicity was measured with a passive hemagglutination assay (PHA), quantified as geometric mean titers (GMTs) and seroconversion rates. The safety of the vaccine was investigated by determining adverse reactions occurring within 4 h, 3 days, and 1 month after injection. The seroconversion rate for children and adults 1 month after vaccination was 96.92% and 89.02%, respectively. In the case of children, the GMTs of Vi antibodies before vaccination were 5.87 +/- 1.34 and 142.59 +/- 2.39 at one month after vaccination. For adults, the GMTs before and one month after vaccination were 5.58 +/- 1.28 and 58.56 +/- 3.67, respectively. Vi antibodies persisted for as long as 6 and 12 months after vaccination. All adverse reactions in adults and children were minor and did not require treatment. The Vi CPS vaccine was safe and immunogenic in adults and children older than 5 years.     

Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults

BackgroundThis Phase IV study evaluated the safety and immunogenicity of a two-dose, MF59^®-adjuvanted (Novartis Vaccines, Marburg, Germany), monovalent, A/H1N1 pandemic influenza vaccination schedule in Human Immunodeficiency Virus (HIV) positive children and young adults.MethodsA total of 83 children infected with HIV-1, and 37 non-immunocompromised, age-matched controls were enrolled. All participants received two vaccine doses administered three weeks apart. Antibody responses were assessed by haemagglutination assay at baseline, three weeks after each vaccine dose, and six months after immunization. Vaccines were evaluated according to European influenza vaccine licensure criteria.ResultsThe investigational vaccine was well tolerated. After the first vaccine dose, seroconversion rates were significantly lower in HIV-positive patients (60%) than controls (82%), with GMTs of 419 and 600, respectively. No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose. Persisting antibody titers were similar for both HIV-positive and non-infected controls, six months after immunization.ConclusionOne dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children. However, a two-dose vaccination schedule may be optimal for this population.     

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.     

A comparative seroepidemiologic study of the neutralizing antibody against the virulent standard strains and the Sabin vaccine strains of poliovirus among healthy Japanese

The neutralizing antibody of 160 serum specimens collected in 1978 from healthy residents in five prefectures in Japan was titrated against both the virulent standard strains and the Sabin vaccine strains of three types of poliovirus. Antibody-positive rates with both strains of respective types at a level of 1:4 were comparable in all three types of poliovirus. However, the geometric mean titers (GMTs) obtained against both strains showed statistically significant difference depending on the age-cohort's previous history of exposure to the wild or the vaccine strains of polioviruses: the younger age cohorts showed higher GMTs to the Sabin strains, while adults responded higher to the virulent standard strains. The difference was most pronounced in type 1.     

Pneumococcal vaccine immunization of patients with renal impairment

The immunogenicity of the polyvalent pneumococcal vaccine was studied in renal allograft recipients and dialysis patients. There was no significant overall difference in the antibody response of the allograft recipients compared to control subjects at 1 month following immunization. Chronic hemodialysis patients had significantly lower postvaccination antibody levels for 6 of 12 serotypes. Better graft function in the allograft recipients correlated positively with higher antibody levels. Azathioprine and prednisone in dosages employed had no consistent effect on antibody response. No deterioration of renal function ascribable to the vaccine was observed. Patients were sampled at 1, 2, and 3 1/2 years following immunization. Geometric mean titers (GMT) were calculated for all the serotypes per group for each time of sampling. There was a significant decrease with time in antibody GMTs for all the groups (P less than 0.01). Chronic hemodialysis patients had significantly lower GMTs than control subjects and allograft recipients at 1, 2, and 3 1/2 years postimmunization (P less than 0.05). The 3 1/2 years postimmunization antibody levels were very low in dialysis patients, suggesting that reimmunization of these patients may be required.     

Diphtheria-Tetanus-Pertussis Immunization by Intradermal Jet Injection

An intradermal jet injector was used to administer combined diphtheria, tetanus, and pertussis (D.T.P.) vaccines to infants aged 2 to 12 months. A second dose was given one month after the first and a third six months after the second. Each dose was considerably smaller than the standard intramuscular dose. Blood samples taken one month after the third dose showed a satisfactory diphtheria and tetanus antitoxin response in all but a few cases. The antibody response to the pertussis component was not examined. Reactions were insignificant. Intradermal jet injection is proposed as a cheap, extremely rapid, and effective technique for D.T.P. immunization, especially suitable for use in remote areas where trained staff and facilities are few and many children require immunization.     

Antibody responses of Macaca fascicularis against a new inactivated polio vaccine derived from Sabin strains (sIPV) in DTaP-sIPV vaccine

Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans.     

乙型肝炎血源疫苗皮内接种4年效果观察

为了解乙型肝炎血源疫苗皮内接种的持久效果,选ＨＢｓＡｇ、抗－ＨＢｓ和抗－ＨＢｃ均（－）的９～１１岁儿童１０３名,随机分成４组,分别皮内接种１μｇ×４和３μｇ×４（均按０,１,２,５月程序）和肌肉接种１０μｇ×３和３０μｇ×３（各按０,１,２月程序）。首针后４８月时,１μｇ、３μｇ、１０μｇ和３０μｇ组抗－ＨＢｓ≥１０ｍＩＵ／ｍＩ者各为６９．２％,８０．０％、９２．３％和８１．８％;ＧＭＴ则为１４．５,７９．０,４４．８和７０．９ｍＩＵ／ｍｌ,３μｇ×４皮内免疫的近期和远期效果与肌肉组３０μｇ×３相似,宜于某些人群采用     

The trend of acquired immunity with live poliovirus vaccine and the effect of revaccination: follow-up of vaccinees for ten years

The persistence of neutralizing antibody (NA) against three types of poliovirus acquired after two doses of trivalent live attenuated poliovirus vaccine (LPV) has been followed up for ten years in individual vaccinees. Sixty-seven children were bled once a year over a five year period following the primary vaccination. More than 80% of them retained NA against all three types of poliovirus. Thirty-two individuals whose NA titres were 1:16 or over for types 1 and 2 and 1:4 or over for type 3 at the fifth year were further followed up for a further five years and it was shown that during this period some of them had a naturally-acquired antibody rise, mostly against type 3 virus. At the sixth to eighth year after the primary vaccination, one further dose of the trivalent vaccine was administered to the children whose NA titres were down to 1:8 or less and the effect of booster vaccination on NA was followed. Other subjects were revaccinated with LPV and their fecal excretion of the vaccine virus was investigated. The results showed that a decrease in serum antibody level could be a good indicator of the local resistance of the alimentary tract and that reinfection could occur if serum NA had decreased to 1:8 or less, which allowed a virus excretion in the stools.     

Studies of the Neutralizing Activity and Avidity of Anti-Human Immunodeficiency Virus Type 1 Env Antibody Elicited by DNA Priming and Protein Boosting

DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.