成人和儿童接种国产甲型肝炎灭活疫苗的安全性与免疫原性的初步观察

为了评价国产甲型肝炎 (甲肝 )灭活疫苗的安全性和免疫原性 ,将 176名健康易感儿童和 2 0 6名成人随机分为 4组 ,10 7名儿童 (A组 )和 131名成人 (B组 )接种国产甲肝灭活疫苗 ,另 6 9名儿童 (C组 )和 75名成人 (D组 )作为对照接种史克必成公司生产的甲肝灭活疫苗。国产疫苗剂量为儿童 6 4 0EU/1 0ml,成人 12 80EU/1 0ml;对照疫苗剂量儿童 72 0EIU/1 0ml,成人 14 4 0EIU/1 0ml,均采用 0、6个月免疫程序。观察 72h内局部和全身反应 ,免疫后 1、6、7个月的免疫应答水平。结果显示 :所有接种对象均未出现明显的局部和全身副反应 ,亦未发现免疫后丙氨酸氨基转移酶 (ALT)升高。初次免疫后 1个月 ,A组和B组抗体阳转率分别为 94 8%和 96 7% ,几何平均滴度(GMT)为 75 8 6mIU/ml和 36 30 8mIU/ml。全程免疫后 1个月 ,4个组抗体阳转率均为 10 0 % ,A组和B组抗体GMT升至 10 4 71 2mIU/ml和 12 30 2 7mIU/ml,略高于对照的C组和D组 (分别为 30 90 3mIU/ml和3388 4mIU/ml)。表明国产甲肝灭活疫苗具有良好安全性和免疫原性。     

国产甲乙型肝炎联合疫苗的安全性和免疫原性初步研究

目的评价国产甲、乙肝联合疫苗的安全性和免疫原性。方法对278名健康儿童和312名健康成人接种国产甲、乙肝联合疫苗，并与单价甲肝灭活疫苗和乙肝灭活疫苗进行对照，观察其免疫后的副反应和检测抗体阳转率。结果接种国产甲、乙肝联合疫苗成人和儿童中均未观察到严重全身反应和局部反应。首针免疫后7个月，儿童组甲肝抗体和乙肝抗体阳转率分别达到100％和96．88％，GMT达到29144mIU／ml和102mlU／ml；成人组甲肝抗体和乙肝抗体阳转率也达到100％和98．84％，GMT达到21891mIU／ml和112mlU／ml。儿童和成人接种甲乙肝联合疫苗后，甲肝和乙肝抗体阳转率和GMT均高于单价疫苗。结论国产甲、乙型肝炎联合疫苗是安全的，并可诱导较高的甲肝抗体和乙肝抗体应答。     

甲型肝炎灭活疫苗（Vero细胞）人体接种的安全性和免疫原性研究

目的 研究在中国儿童和成人中接种江苏延申生物科技股份有限公司研制的甲型肝炎灭活疫苗(Vero细胞)的安全性和免疫原性.方法 在广西蒙山县筛选甲型肝炎病毒易感者,采用随机、盲法,同类疫苗对照方法,对600名1.5～15岁儿童和600名成人按照2:1比例,各400人接种试验疫苗(儿童或成人剂量甲型肝炎灭活疫苗)和200人接种对照疫苗(市售同类儿童或成人剂量甲型肝炎灭活疫苗),免疫程序为0、6月;观察接种后局部反应和全身反应;采用EIA竞争抑制法检测免疫前后的甲型肝炎抗体,以WHO甲肝免疫球蛋白(含100IU/ml)标准品进行标定,计算免疫后的甲型肝炎抗体阳转率和抗体几何平均滴度(mIU/ml).结果 两剂量组试验疫苗与对照疫苗的局部反应和全身反应相似,局部反应以注射部位疼痛多主,全身反应以轻度发热反应较常见.试验疫苗儿童剂量组和成人剂量组甲肝抗体阳转率分别为98.53%和97.55%,甲肝抗体几何平均滴度分别为10 332.32 mIU/ml和9 473.65 mIU/ml,与对照组比较均无显著差异.结论 新型甲肝灭活疫苗(Vero细胞)儿童剂量(800EU/ml)和成人剂量(1 600EU/ml)对儿童或成人接种的安全性良好,并可诱导高度的抗HAV阳转率和抗体水平.     

国产甲型肝炎灭活疫苗在低龄儿童中应用的安全性和免疫原性研究

目的 探讨国产甲型肝炎灭活疫苗在低龄儿童（1－4岁）中应用的安全性和免疫原性。方法 选1－4岁易感健康儿童63名，随机分为两组，按0，3和0，6程序接种国产甲肝灭活疫苗500U／剂，观察免疫后的局部和全身反应，并检测初免后及全程免疫后的抗－HAV阳转率和抗体GMT。结果 初免和加强免疫后有轻微的过性局部和全身反应，未见肝功异常。初免后1、3、6个月抗体阳转率分别为85.7%、88.5%和83.8%；抗体GMT玢别为182mU/ml、225mU/ml和252mU/ml；0，3和0，6程序全程免疫后1个月抗体阳转率均为100％；抗体GMT分别为2718mU/ml和4683mU/ml。结论 国产甲肝灭活疫苗在低龄儿童中应用具有良好的安全性和免疫原性；接种两剂可获高滴度甲肝抗体；0，6程序优于0，3程序。     

孩尔来福甲型肝炎灭活疫苗0,12个月免疫程序研究

目的　对孩尔来福 (HealiveR○)甲型肝炎 (甲肝 )灭活疫苗的安全性、免疫原性及适宜儿童的剂量进行研究。方法　在某山区两个农村筛选 4～ 10岁甲肝病毒抗体 (抗 HAV)阴性的 85名易感儿童。以自然村随机分为两组 ,按 0 ,12个月免疫程序分别接种北京科兴生物制品有限公司生产的每剂 2 50U 0 .5ml和 50 0U 1ml甲肝灭活疫苗 ,观察免疫后局部反应和全身反应 ,检测初次免疫 (初免 )后 2 1天、12个月及全程免疫后 1个月抗 HAV阳转率和抗体几何平均滴度 (GMT )。结果　两组均未见严重局部反应和全身反应 ;2 50U 0 .5ml组和 50 0U 1ml组初免后 2 1天 ,抗 HAV阳转率分别为94.4%和 10 0 .0 % ,GMT分别为 195mIU ml和 3 70mIU ml ;初免后 12个月抗 HAV全部阳转 ,GMT分别达 3 61mIU ml和 456mIU ml(P >0 .0 5) ;全程免疫后 1个月 ,GMT分别达 14 893mIU ml和2 1696mIU ml。结论　孩尔来福甲肝灭活疫苗的安全性和免疫原性好 ;每剂 2 50U 0 .5ml适宜儿童 ;0 ,12个月免疫程序更适宜中国儿童     

孩尔来福甲型肝炎灭活疫苗接种乙型肝炎病毒表面抗原阳性儿童的研究

为进一步观察孩尔来福 (Healive)甲型肝炎 (甲肝 )灭活疫苗在乙型肝炎病毒表面抗原 (HBsAg)阳性儿童中接种的安全性和免疫原性 ,于 2 0 0 1年在平山县农村 ,将 4 2例HBsAg阳性儿童随机分为 4组 ,分别按照 0、1,0、3,0、6 ,0、12个月程序接种Healive甲肝灭活疫苗 ,观察初免和全程免疫后的局部和全身反应 ,检测初免及全程免疫后 1个月血清抗甲肝病毒抗体 (抗 HAV)阳转率和滴度。结果显示 :初免和全程免疫后 72h内均未见局部和全身反应 ,亦无丙氨酸氨基转移酶 (ALT)异常 ;4个组初免后 1个月 ,抗 HAV阳转率均达 10 0 0 % ,抗体几何平均滴度 (GMT)为173mIU/ml～ 318mIU/ml,其差异无显著的统计学意义 (t=1 2 0 4 ,P >0 0 5 )。全程免疫后 1个月 ,0、12 ,0、6 ,0、3,0、1个月免疫程序组GMT分别为 192 99mIU/ml、4 30 1mIU/ml、2 74 9mIU/ml、172 5mIU/ml,与同龄健康易感儿童按相同免疫程序的免疫效果规律一致。全程免疫后 1个月 ,HBsAg阳性儿童和健康儿童抗 HAVGMT的差异无显著的统计学意义 (P >0 0 5 )。表明HBsAg对Healive甲肝灭活疫苗的免疫应答无干扰 ;HBsAg阳性儿童接种Healive甲肝灭活疫苗是安全和有效的。     

国产甲型肝炎灭活疫苗在儿童中应用的安全性免疫原性和免疫程序研究

为了评价国产甲型肝炎(甲肝)灭活疫苗在儿童中应用的安全性、免疫原性和免疫程序,在河北省某地山区农村筛选5～15岁的甲肝易感儿童275人,以村为单位,随机分为4组,分别接种1 000U/剂和500U/剂(0、3个月和0、6个月程序),观察初种和加强免疫后局部反应和全身反应,检测免疫后1、3、4、6、7个月的血清抗甲肝病毒抗体(抗-HAV)阳转率和滴度.结果显示国产甲肝灭活疫苗无严重的局部及全身反应,1 000U/剂和500U/剂初免后1个月抗-HAV阳转率分别为93.8%和90.6%,抗体滴度分别为174mIU/ml和146mIU/ml;全程免疫后1个月各组抗体阳转率均为100.0%,1 000U组和500U组抗-HAV滴度分别为7 540mIU/ml、4 535mIU/ml;500U组0、6个月和0、3个月程序免疫后抗-HAV滴度分别为4 535mIU/ml和3 269mIU/ml,两组比较差异有极显著的统计学意义.表明国产甲肝灭活疫苗在儿童中应用是安全、有效的,500U/剂适用于儿童,免疫程序以0、6个月为佳.     

孩尔来福甲型肝炎灭活疫苗不同免疫程序的评价

为评价孩尔来福 (Healive○R)甲型肝炎 (甲肝 )灭活疫苗不同免疫程序的免疫原性 ,在山区农村的 5个村 ,对 16 7名 5～ 11岁甲肝易感儿童 ,分 5组以 0、1,0、3,0、6 ,0、12个月程序接种Healive○R甲肝灭活疫苗 (2 5 0U/剂 ) ,对照组以0、6个月程序接种HavrixTM72 0EIU甲肝灭活疫苗。结果显示 :Healive○R甲肝灭活疫苗初次免疫 (初免 )后 2周、4周抗甲肝病毒抗体 (抗 HAV)阳转率分别为 97 0 %和 95 5 % ,几何平均滴度 (GMT)分别为 35 5mIU/ml和 2 5 1mIU/ml;初免后 3、6、12个月的抗 HAV阳转率均为 10 0 0 % ;GMT则分别为 4 17mIU/ml、391mIU/ml和 36 1mIU/ml。各程序组全程免疫后 1个月抗 HAV阳转率均为 10 0 0 % ;GMT则分别为 14 893mIU/ml(0、12个月 ) >5 96 3mIU/ml(0、6个月 ) >32 6 5mIU/ml(0、3个月 ) >1973mIU/ml(0、1个月 ) ,差异有非常显著的统计学意义。HavrixTM 甲肝灭活疫苗初免后 4周、6个月和全程免疫后 1个月 ,抗 HAV阳转率分别为 71 0 %、71 0 %和 10 0 0 % ,GMT为 15 8mIU/ml、15 2mIU/ml和 110 4mIU/ml。免疫 1剂Healive○R甲肝灭活疫苗GMT可达有效保护水平的 12倍以上。 0、1个月程序可用于特殊人群的加速免疫 ,0、3,0、6 ,0、12个月程序可根据不同人群的需求而灵活应用 ,以 0、1     

孩尔来福甲型肝炎灭活疫苗在儿童中应用的安全性和免疫原性观察

为探讨孩尔来福 (Healive)甲型肝炎 (甲肝 )灭活疫苗在儿童中应用的安全性和免疫原性 ,选择 2～ 15岁抗甲肝病毒抗体 (抗 HAV)阴性健康易感儿童 91名作为接种对象 ,采用 0、6个月程序接种Healive甲肝灭活疫苗 2 5 0U/剂 ,观察免疫后的局部和全身不良反应 ,并于全程免疫后 1个月检测抗 HAV阳转率和抗体几何平均滴度 (GMT)。结果显示 :91名观察对象在接种第 1针和第 2针后均未见严重不良反应 ,仅在 8～ 72h出现轻微的一过性局部和全身轻度发热反应。全程免疫后 1个月抗 HAV阳转率为 10 0 % ,抗体GMT为 14 4 0 7mIU/ml。表明Healive甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性 ,采用 0、6个月免疫程序可获得高滴度抗体。     

孩尔来福甲型肝炎灭活疫苗单剂接种安全性与免疫效果观察

为探讨孩尔来福 (Healive○R)甲型肝炎 (甲肝 )灭活疫苗在人群中应用的安全性和免疫原性 ,选择 2 4～ 36月龄、18～ 2 5岁 2组人群 ,分别接种Healive○R甲肝灭活疫苗 2 5 0U、5 0 0U1针 ,观察免疫后的局部和全身反应 ,并检测儿童免疫后 6周抗体阳转率和抗体几何平均滴度 (GMT)。结果发现 :接种后仅个别人有轻微的一过性全身反应 ,抗体阳转率为 94 5 2 % ,抗体GMT为 2 6 0 3mIU/ml。显示Healive○R甲肝灭活疫苗在人群中接种具有良好的安全性和免疫原性。     

倍尔来福TM甲、乙型肝炎联合疫苗安全性和免疫原性研究

目的 观察倍尔来福~(TM)甲、乙型肝炎(甲、乙肝)联合疫苗的安全性和免疫原性。方法以高中一年级(成人组)和小学1～5年级(儿童组)学生为研究对象,按对甲、乙肝病毒均易感、只对甲肝病毒易感和只对乙肝病毒易感分为AB组、A组和B组,按0、1和6个月三剂程序分别接种甲、乙肝联合疫苗、灭活甲肝疫苗和重组乙肝疫苗。疫苗剂量成人组每剂含甲肝病毒抗原500U和(或)HBsAg10μg,儿童组减半。疫苗接种后72h内观察副反应,免疫后2、7个月采集血清标本检测抗-HAV和抗-HBs。结果 儿童AB组和成人AB组局部副反应发生率分别为0.58％(2/344)和2.56％(8/312),全身副反应发生率分别为9.88％(34/344)和5.45％(17/212),与对照组相比差异无显著性。局部反应主要是轻度疼痛,全身反应主要是低热。免疫后7个月,两组抗-HAV阳转率均为100％,与A组相同;抗体滴度(GMT)分别为33 910mIU/ml和23 435 mIU/ml,显著高于A组;两组抗-HBs阳转率分别为97.30％和96.63％;GMT为103 mIU/ml和102 mIU/ml,抗-HBs阳转率及GMT均与B组差异无显著性。结论 倍尔来福~(TM)甲、乙肝联合疫苗与单价甲肝灭活疫苗和单价重组乙肝疫苗具有相同的安全性和免疫原性。     

精制甲型肝炎灭活疫苗(Vero细胞)维罗信TM的安全性和免疫原性随机对照研究

目的评价精制甲型肝炎灭活疫苗(Vero细胞)的安全性和免疫原性。方法2005年1～8月在广西恭城县选择1507名健康人群,以随机、双盲、平行对照方法,观察该疫苗的不良反应,抗体阳转率和抗体水平(GMT),应用EIA竞争抑制法检测血清抗甲型肝炎抗体(抗-HAVIgG)。结果成人剂量组试验疫苗全身、局部反应发生率分别为8.80%、2.67%,与对照疫苗(分别为12.41%、4.41%)相比,无显著差异;儿童剂量组试验疫苗全身、局部反应发生率分别为10.60%、2.28%,与对照疫苗(10.71%、2.86%)相比,亦无显著性差异。维罗信首针免疫后1个月,儿童剂量组和成人剂量组的阳转率分别为88.2%、93.8%,两针全程免疫1个月后两组抗体阳转率均达到100%,抗体滴度分别为16447、8555mIU/ml,对照疫苗分别为1946、5881mIU/ml,儿童剂量组抗体滴度与对照组相比有显著性差异。结论精制甲型肝炎灭活疫苗(Vero细胞)在儿童和成人中应用具有良好的安全性,采用0,6个月免疫程序免疫后抗体阳转率达100%,并有高的抗体滴度。     

Immunological priming of one dose of inactivated hepatitis A vaccine given during the first year of life in presence of maternal antibodies

BACKGROUND: In hepatitis A virus (HAV)-seronegative infants, inactivated hepatitis A vaccines are highly immunogenic. On the contrary, in infants who are HAV-seropositive before vaccination, the interfering effect of passively-transferred maternal anti-HAV antibodies leads to lower post-primary immunization anti-HAV levels, as compared to those achieved by seronegative infants. One possible way to overcome this drawback is to delay hepatitis A vaccination later during the first year of life. The objective of the study was to document the immunogenicity of an inactivated hepatitis A vaccine in 6 months old HAV-seropositive infants, given as two dose regimen consisting of a single primary immunization at 6 months of age, followed by a booster dose 6 months later. METHODS: The immunogenicity of one hepatitis A vaccine (Avaxim pediatric, Aventis Pasteur) was documented in 108 6 months old, HAV-seropositive infants randomly assigned to receive one priming dose of hepatitis A vaccine either concomitantly with (Group 2) or 2 weeks after the third dose of routine diphteria-tetanus-whole cell pertussis reconstituting lyophilized tetanus conjugated Haemophilus influenzae type b (DTwcP//PRP approximately T) vaccine and oral poliomyelitis vaccine (OPV) (Group 1). A booster dose was given 6 months later, concomitantly with MMR vaccine. RESULTS: The 91 infants who were HAV-seropositive (ELISA titer >20 mIU/ml) at the moment of primo vaccination remained seropositive 1 month later. Geometric mean titers (GMT) decreased from 292 and 278 mIU/ml 1 month after the first dose, to 77.6 and 76.0 mIU/ml 6 months after, in Groups 1 and 2, respectively. Post-booster titers increased markedly in both groups, with GMTs of 1731 and 1866 mIU/ml and geometric mean post/pre-immunization titer ratios of 22.3 and 24.6, respectively. CONCLUSIONS: These results suggest that immunological priming induced by a single dose of Avaxim pediatric administered to 6 or 6.5 months old, HAV-seropositive infants is present and should not preclude the use of this vaccine in such populations.     

甲型肝炎减毒活疫苗与灭活疫苗不同免疫程序免疫后7年血清学效果观察

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。     

Comparative immunogenicity and safety of two dosing schedules of a combined hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised study

An open, randomised study was undertaken to demonstrate the equivalence in immunogenicity and to determine the reactogenicity and safety of two dosing schedules (0, 6 or 0, 12 month) of an adult formulation of a combined hepatitis A and B vaccine containing 720 EL.U. of inactivated hepatitis A antigen and 20 μg of hepatitis B surface antigen (Twinrix™, SmithKline Beecham Biologicals, Belgium) in 240 healthy volunteers aged 12–15 years. The vaccine was well tolerated when administered using either vaccination schedule. At month 7, 98.1% of subjects completing the 0, 6 month vaccination schedule were seroprotected against hepatitis B (anti-hepatitis B surface antigen (anti-HBs)10 mIU/ml) and 100% were seropositive for anti-hepatitis A virus (anti-HAV) antibodies (i.e., 33 mIU/ml). The corresponding geometric mean titres (GMTs) were 2791 mIU/ml for anti-HBs and 5992 mIU/ml for anti-HAV antibodies. At month 13, 97% of subjects assigned to the 0, 12 month vaccination schedule were protected against hepatitis B and 99% were seropositive for anti-HAV antibodies. The corresponding GMTs were 4340 and 8472 mIU/ml, respectively. A combined response (i.e., subjects, who were seropositive for anti-HAV antibodies and seroprotected for anti-HBs antibodies) was achieved in 98% of subjects vaccinated according to the 0, 6 month interval and in 96% of subjects vaccinated using the 0, 12 month schedule. The reactogenicity of both vaccination schedules was also equivalent. The results thus show that the combined hepatitis A and B vaccine can be administered using flexible vaccination intervals, which make it suitable for use in large-scale hepatitis immunisation programmes.     

Comparison of immunogenicity of two hepatitis A vaccines--VAQTA and HAVRIX--in young adults.

Two new hepatitis A vaccines have been developed, and their immunogenicity tested using different immunoassays. The present study was designed to compare the immunogenicity of these two hepatitis A virus (HAV) vaccines--VAQTA and HAVRIX--as determined by seroconversion rates and anti-HAV titers, and using the same immunoassay. Healthy volunteers (15-30 y), seronegative for anti-HAV, were randomized in an open single center study to four groups of 20-21 vaccinees each, to receive either a 25 U or a 50 U dose of VAQTA, or HAVRIX at 720 EU or 1440 EU/dose, administered at 0, 1 and 6 m or at 0 and 6 m, respectively. Four weeks after primary immunization, seroconversion rates were 100% for VAQTA and 95% for HAVRIX, following injection of 50 U or 1440 EU, respectively (p = NS) and anti-HAV GMTs were 40 and 37 mIU/ml for VAQTA and HAVRIX, respectively. At 6 months, prior to the booster dose, seroconversion rates were 100% for both vaccines, with anti-HAV GMTs of 111 and 70 mIU/ml for VAQTA and HAVRIX, respectively (P < 0.05). At month 7, four weeks after the only booster injection, using the two dose regimen, anti-HAV titers were 2212 and 1511 mIU/ml for VAQTA and HAVRIX, respectively (P < NS). Using three doses of 25 U/dose of VAQTA or 720 EU/dose of HAVRIX at 0, 1 and 6 m did not produce any clinically evaluable advantage over the two dose regimen for either vaccine. No significant adverse events were observed using either vaccine. In summary, both vaccines have similar immunogenicity demonstrated using identical immunoassays for evaluation. These results also confirm the outstanding immunogenicity of a single dose of either of the HAV vaccines and support their use in pre- and possibly postexposure prophylaxis against hepatitis A virus infection.     

Immunogenicity and safety of a pediatric dose virosomal hepatitis A vaccine in Thai HIV-infected children

The immunogenicity and safety of a pediatric dose of a virosomal hepatitis A vaccine (Epaxal?) was evaluated in a group of 45 Thai children with human immunodeficiency virus (HIV) infection, age 2-16 years. Vaccines were administered at 0 and 6 months. Anti-HAV antibody titers were measured at baseline (before injection) 1 and 7 months after primary vaccination. The prevalence of HAV protective antibody in 45 Thai HIV-infected children was 13.6%. The seroprotection rate was 71% at 1 month and 100% at 7 months. The booster dose increased geometric mean concentration (GMC) from 106.5 mIU/ml to 3486.1 mIU/ml. Higher CD4 lymphocyte counts at enrollment was a predictive factor for HAV antibody response. Both doses of Epaxal? were well tolerated. These preliminary data suggest that a pediatric dose of Epaxal? is an effective hepatitis A vaccine for HIV-infected children and should be considered for implementation on a larger scale in the pediatric HIV population.