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1.
目的 探讨不同剂量配比的Sabin株脊髓灰质炎灭活疫苗(Sabin IPV)基础免疫后中和抗体的持续时间及加强免疫前后中和抗体水平的变化.方法 用不同配比的Ⅰ、Ⅲ型脊髓灰质炎病毒原液制备两批Sabin IPV,并使用GSK制备的DTaP-w IPV作为阳性对照组,对18只Wistar大鼠进行3针基础免疫后,每间隔3个月采血直到加强免疫前,并同时于加强免疫后1个月采血,并对血清中抗脊髓灰质炎病毒3个型别的中和抗体效价进行初步研究.结果 大鼠采用0、1、2月免疫程序进行3针免疫后,Ⅰ、Ⅱ、Ⅲ型脊髓灰质炎病毒中和抗体的几何平均滴度随着时间的变化均有所下降,但绝大部分组大鼠的血清中和抗体阳转率仍维持在100%,在加强免疫后,各组的三个型别的中和抗体水平在短期内明显升高.结论 Sabin IPV有良好的免疫持久性,并在加强免疫后,可产生更高水平的中和抗体. 相似文献
2.
目的 研究铝佐剂和免疫程序对不同配比的Sabin IPV免疫原性的影响.方法 用Ⅰ、Ⅱ、Ⅲ型脊髓灰质炎病毒原液制备四批Sabin IPV,分别为中剂量无佐剂组、中剂量铝佐剂组、低剂量无佐剂组、低剂量铝佐剂组,采用0、1、2月和0、2、4月两种免疫程序对大鼠进行3针基础免疫,每针基础免疫一个月后采血,并检测免疫后血清中3个型别的中和抗体水平.结果 经过3针基础免疫后,各组Ⅰ、Ⅱ、Ⅲ中和抗体几何平均滴度均显著提高,阳转率均达到100%.对不同组别间两种免疫程序比较无显著差异,但相同条件下,0、2、4月免疫程序可诱导产生更高的抗体水平.对相同免疫程序下不同组别进行比对,添加铝佐剂组与无佐剂组相比可以诱导更高的抗体水平.结论 铝佐剂和免疫程序可提高Sabin IPV免疫原性. 相似文献
3.
目的 了解福建省实施口服脊髓灰质炎减毒活疫苗(OPV)常规免疫和强化免疫活动以来健康人群脊髓灰质炎抗体水平,为人群免疫策略、维持无脊灰状态提供科学依据.方法 应用微量细胞中和试验法对5个地区人群进行脊髓灰质炎抗体水平检测,建立数据库,SPSS统计软件进行统计分析.结果 共检测400名1~59岁人群的血清标本,脊灰Ⅰ、Ⅱ、Ⅲ型抗体阳性率分别为99.0%、99.3%、97.5%,几何平均滴度(GMT)Ⅰ、Ⅱ、Ⅲ型分别为1∶79.1、1∶31.2、1∶24.7;各型抗体GMT均随年龄增长呈下降趋势.结论 福建省通过OPV常规免疫和强化免疫活动后,健康人群对脊灰已形成免疫屏障.各型抗体GMT随年龄增长呈下降的趋势应引起重视. 相似文献
4.
目的检测二苯氧乙醇对3价减毒株脊髓灰质炎灭活疫苗(Sabin IPV)效力的影响及其毒性。方法将每毫升(每剂量)含二苯氧乙醇5、7mg的Sabin IPV分别放在4℃、37℃2和7d,用ELISA方法检测病毒D抗原含量,并进一步测定小鼠和豚鼠的免疫反应。按《中国生物制品规程通则异常毒性试验规程》检测其毒性。结果含两种浓度二苯氧乙醇的Sabin IPV于37℃保存2、7d,两种疫苗中的Ⅰ、Ⅱ、Ⅲ型D抗原含量、中和抗体的效价与不含二苯氧乙醇的对照组相比,无明显差异。观察期内,小鼠和豚鼠全部健存,没有异常反应。结论二苯氧乙醇对Sabin IPV效力没有影响,安全性好,可以作为Sabin IPV的防腐剂。 相似文献
5.
研究灭活SARS病毒的免疫原性。SARS病毒F6 9株经甲醛灭活后 ,加入氢氧化铝佐剂 ,以 3种剂量接种BALB/c小鼠 ,定时采血 ,测定特异性抗体的滴度及其中和活性 ,同时用化学发光酶联免疫法测定抗血清与SARS病毒结构蛋白的反应特异性及其相对强度。结果发现 ,小鼠接种疫苗 4d后 ,血清中可检测到IgM抗体 ,直至 2 6d后逐渐下降 ;IgG抗体在初次免疫 8d后出现 ,4 7d时达最高峰 ,6 3d后进入稳定期 ;不同剂量组的抗体滴度具有明显剂效关系 ,低剂量组和中剂量组滴度峰值为 1∶192 0 0 ,高剂量组滴度峰值为 1∶384 0 0。中和实验结果表明 ,小鼠所产生的抗体具有中和病毒活性 ,在 6 3d时 ,低剂量组和中剂量组血清的中和效价为 1∶12 80 ,高剂量组血清的中和效价为 1∶5 12 0。抗体分类结果表明 ,小鼠抗血清中含有针对多种SARS病毒结构蛋白的特异性抗体 ,其中 ,针对N蛋白、S4蛋白和S2蛋白的抗体水平相对较高 ,而抗M抗体、抗 3CL抗体的水平相对较低。上述结果说明 ,SARS病毒F6 9株经甲醛灭活后 ,各主要结构蛋白仍保持较强免疫原性 ;免疫小鼠后 ,可以诱导产生高滴度的特异性混合抗体 ,在体外可以保护敏感细胞不受SARS病毒攻击 相似文献
6.
目的 构建H5 N1亚型禽流感病毒株密码子优化的血凝素(HA)DNA疫苗并研究其免疫原性。方法 应用MacVector软件分析H5N1亚型禽流感病毒A/Viet Nam 1203/04株HA(H5-VN HA)基因序列,对这些序列进行密码子优化处理,人工合成优化后的H5-VN HA基因。将密码子优化H5-VN HA基因与pSW3891质粒连接,并以人组织纤维蛋白溶酶原激活剂(tPA)信号肽取代H5-VN HA信号肽,构建成表达H5-VN HA基因的重组质粒,命名为HA-VN.tPA(即密码子优化的H5-VN HA基因DNA疫苗)。以HA-VN.tPA转染293T细胞,应用蛋白质印迹法检测转染细胞中HA蛋白的表达。以HA-VN.tPA对2只新西兰兔进行DNA免疫,用ELISA方法检测分析免疫后兔血清中HA特异性抗体的产生。结果 密码子优化的H5-VN HA基因中哺乳动物细胞偏爱的密码子频率高于野生型H5-VN HA基因。蛋白质印迹法分析结果表明,HA-VN.tPA转染293T细胞后,细胞裂解液中检测出HA蛋白的表达。ELISA分析结果表明,以HA-VN.tPA免疫3次后,实验兔体内产生了较高水平的HA特异性抗体(血清中平台期抗体滴度达1:13 500)。结论 成功构建了H5N1亚型禽流感病毒密码子优化的HA 基因DNA疫苗,该疫苗可引导免疫后宿主体内产生高滴度特异性抗体。 相似文献
7.
目的 构建脊髓灰质炎病毒疫苗株Sabin Ⅰ的全基因序列克隆.方法 利用分子生物学技术,通过分段扩增和酶切连接逐步构建插入脊髓灰质炎病毒疫苗株Sabin Ⅰ全基因序列的质粒,采用单引物二次PCR法引入点突变,并通过酶切、测序等方法进行鉴定.结果 在pWSK29载体中成功插入脊髓灰质炎病毒疫苗株Sabin Ⅰ全基因序列,酶切鉴定正确,序列测定显示有9个核苷酸变异.结论 成功构建脊髓灰质炎病毒疫苗株Sabin Ⅰ的全基因序列克隆,为进一步改造并研究其功能特别是3D聚合酶的功能打下了基础. 相似文献
8.
改良Lowry法测定Sabin株脊髓灰质炎灭活疫苗蛋白质含量的研究 总被引:1,自引:0,他引:1
目的 建立Sabin株脊髓灰质病毒灭活疫苗(Sabin strain inactivated poliovims vaccine,SabinIPV)中微量蛋白质含量测定的方法.方法 采用lowry法结合三氯乙酸沉淀法测定试样中的蛋白质含量,摸索并优化各个实验条件.结果 该方法能够排除Sabin IPV疫苗样品中游离氨基酸、多肽和酚红指示剂等的干扰,线性范围为2.5-40μg/ml,r=0.9998;加标平均同收率为95.32%,批内和批间变异系数均小于10%.结论 三氯乙酸沉淀法结合Lowry法的改良方法可以用于测定生物制品中微量蛋白含量. 相似文献
9.
目的 研究流行性感冒(流感)病毒裂解疫苗的安全性和免疫原性。方法 根据国家食品药品监督管理局2002SL0043号《新药临床研究申请批件》的要求,选择876例观察对象按随机双盲法分成试验组和对照组,观察局部反应和全身反应。用微量血凝抑制(H1)试验检验抗体应答反应,计算抗体阳转率、保护率及几何平均滴度(GMT)增长倍数。结果 试验疫苗和对照疫苗间全身和局部不良反应发生率差异无显著意义;两组间H1抗体阳转率、保护率及H3N2亚型和B型H1抗体GMT增长倍数差异无显著意义;然而,两种疫苗H1N1亚型的H1抗体GMT增长倍数间差异有显著意义。结论 两种疫苗均具有很好的安全性和免疫原性。 相似文献
10.
目的 构建登革病毒1~4型重组亚单位疫苗,分析重组疫苗的免疫原性.方法 利用连接肽将登革病毒1型与2型,3型与4型的外膜蛋白DⅢ基因片段连接在一起,克隆人原核表达载体pET-30a,在大肠埃希菌中表达DEN1/2型、DEN3/4型融合重组蛋白.重组蛋白经高效液相色谱柱分离纯化后,混和免疫小鼠,采用中和实验法测定血清中和抗体效价,同时进行乳鼠体内中和实验,观察中和抗体对乳鼠的免疫保护作用.结果 重组蛋白能诱导小鼠产生针对登革病毒1~4型的中和抗体,平均中和效价分别为1:34.9、1:45.3、1:24.7和1:38.4.中和抗体能保护新生乳鼠免受致死剂量DEN1~4的攻击,保护率分别为100%,100%,83%,83%.结论 构建的重组亚单位疫苗具有良好的免疫原性,能诱导小鼠产生中和抗体,为构建单一四价疫苗提供了实验室依据. 相似文献
11.
目的观察候选无细胞百白破-Sabin株灭活脊髓灰质炎联合疫苗(DTaP-sIPV)在大鼠中的免疫保护效果,为疫苗临床前研究提供依据。方法将候选疫苗DTaP-sIPV、无细胞百白破-灭活脊髓灰质炎-b型流感嗜血杆菌联合疫苗(DTaP-IPV/Hib)、吸附无细胞百白破-b型流感嗜血杆菌联合疫苗(DTaP/Hib)、百日咳疫苗效力参考品(全细胞疫苗,wP)按0、30、60 d 3剂免疫程序免疫Wistar大鼠,检测各组大鼠每剂免疫后的血清中各组分抗体水平。在免疫完成后3周,用百日咳18323株通过气雾攻击的方式感染大鼠。在感染后的第3、7、14、21和28天检测各组白细胞数、肺部菌落克隆形成数以及百日咳疫苗组分抗体变化水平。结果候选疫苗组3剂次免疫完成后PT抗体几何平均滴度(GMT,log2)为16.74,FHA抗体GMT为18.44,PRN抗体GMT为10.75,DT抗体GMT为17.34,TT抗体GMT为17.84,针对3种Sabin脊髓灰质炎病毒株(Ⅰ、Ⅱ和Ⅲ型)的抗体的GMT分别为7.57、8.41和9.70,均达到100%阳转。候选疫苗抗原组分抗体除了PRN和I型IPV外,其他组分抗体水平均与疫苗对照组相比无显著性差异。在基础免疫完成后3周对大鼠进行百日咳杆菌气雾攻击,各疫苗组均表现较好的保护效果,白细胞水平都呈现平稳状态,虽然在肺部也检测到少量细菌定植,但各疫苗组间差异不明显,且在感染后第28天都清除至检测限;而空白对照组在肺部则检测到了大量细菌定植,且在感染后第28天都并未清除至检测限,百日咳特异性的FHA和PRN抗体在感染后的第14天也出现了相应的升高。结论候选疫苗在Wistar大鼠模型上具有较好的免疫保护效果。 相似文献
12.
Shou-Dong Lee Cho-Yu Chan May-Ing Yu Yuan-Jen Wang Full-Young Chang Kwang-Juei Lo Assad Safary 《Journal of medical virology》1997,52(2):215-218
The safety and immunogenicity of inactivated hepatitis A vaccine was evaluated in patients with chronic liver disease. Sixty hepatitis A virus antibody (anti-HAV) seronegative patients A virus antibody (anti-HAV) seronegative patients with chronic liver disease (56 chronic hepatitis B and four chronic hepatitis C) and from 17 to 47 years of age received a dose of 1440 ELISA units of the inactivated hepatitis A vaccine at month 0, and a booster at month 6. Anti-HAV seroconversion (⩾ 33 mlU/mL) was 57.6% (34/59) on day 15, and reached 93.2% (55/59) 1 month after primary vaccination. At month 6, the seropositivity of anti-HAV decreased before the booster to 69.0% (40/58). All vaccinees had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive at month 12. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 158, 264, 74, 1309, and 409 mlU/ml at day 15 and months 1, 6, 7, and 12. Overall, 59.7% (71/119) of the vaccine doses administered were followed by mostly minor reactions. The majority of symptoms reported were local, all of which resolved within 3 days after vaccination. No significant changes in serum liver enzyme levels were detected after vaccination. Thus, an inactivated hepatitis A vaccine was safe in patients with chronic liver disease while the immune response was inferior to that observed in healthy subjects reported in a previous study. J. Med. Virol. 52:215–218, 1997. © 1997 Wiley-Liss, Inc. 相似文献
13.
Yang Huijuan Dai Xiaohu Liu Ze Cai Wei Zhou Jian Ma Lei Song Shaohui Li Weidong Liao Guoyang 《Journal of medical virology》2019,91(1):22-30
To analyze the effects of phenol red at various pH values on the Sabin type 2 inactivated polio vaccine (sIPV2), several biophysical techniques were used to evaluate the particle size and capsid protein for conformation. sIPV2’s size was assessed via transmission electron microscopy and dynamic light scattering. The effects of various pH values (from 4.0 to 7.0) on the biophysical characters of sIPV2 particles in solution were determined by dynamic light scattering and zeta potential. The results clearly indicated that aggregation and instability occurred in the solution of sIPV2 particles at a pH of 6.0. Under similar conditions, by dynamic light scattering and zeta potential, the virus particles in solution showed more dispersion and were stable with the addition of 0.05 mM phenol red. According to circular dichroism and intrinsic tryptophan fluorescence data, it was observed that the secondary and tertiary structures of the sIPV2 particles were more stable with the protection of phenol red. At a pH below 6.0, the sIPV2 solution with phenol red had more D-antigen content, which was confirmed by enzyme-linked immunosorbent assay and rat experiments. These results strongly suggested that phenol red improved the pH stability of the sIPV2. The study indicated the potential of phenol red in preserving vaccine potency of the sIPV2 at various pH values. 相似文献
14.
Rosana Richtmann Ricardo L. Chaves Joo S. Mendona Selia R. Konichi Heloisa P. Mitre Kioko Takei Klaus Dietz Bertram Flehmig 《Journal of medical virology》1996,48(2):147-150
The objective of this study was to characterize the immune response of children after the use of two different vaccine doses and to evaluate whether vaccination benefits children attending day care centers in areas with high anti-HAV seroprevalence. The study was conducted in a day care center with a stable population in São Paulo, Brazil. Two groups of 20 children, all seronegative for hepatitis A antibodies, were assigned randomly to receive three times 0.5 and 1.0 ml of the vaccine, the second and third dose 1 and 6 months after the first dose, respectively. There were 27 children in the control group. All children in both vaccinated groups had protective levels of antibodies in the serum after two inoculations, and serious adverse reactions were not observed. In the eighth month of follow-up, a hepatitis A outbreak occurred in the day care center. Five children in the control group had high titers of IgM class anti-HAV, four with clinical manifestations of acute hepatitis. None of the vaccinated children developed symptoms or signs of hepatitis (P = 0.0125), and the estimate of vaccine efficacy was 100%. Two nonstudy children from the center also had clinical and serological evidence of acute hepatitis A. It is concluded that vaccination represents an important method for prevention of hepatitis A transmission in day care centers. The results of this pilot study justify further testing in larger groups. © 1996 Wiley-Liss, Inc. 相似文献
15.
Dedepsidis E Karakasiliotis I Paximadi E Kyriakopoulou Z Komiotis D Markoulatos P 《Virus genes》2006,33(2):183-191
In the present study, a genomic analysis of full VP1 sequence region of 15 clinical re-isolates (14 healthy vaccinees and
one bone marrow tumor patient) was conducted, aiming to the identification of mutations and to the assessment of their impact
on virus fitness, providing also insights relevant with the natural evolution of Sabin strains. Clinical re-isolates were
analyzed by RT-PCR, sequencing and computational analysis. Some re-isolates were characterized by an unusual mutational pattern
in which non-synonymous mutations outnumbered the synonymous ones. Furthermore, the majority of amino-acid substitutions were
located in the capsid exterior, specifically in N-Ags, near N-Ags and in the north rim of the canyon. Also mutations, which
are well-known determinants of attenuation, were identified. The results of this study propose that some re-isolates are characterized
by an evolutionary pattern in which non-synonymous mutations with a direct phenotypic impact on viral fitness are fixed in
viral genomes, in spite of synonymous ones with no phenotypic impact on viral fitness. Results of the present retrospective
characterization of Sabin clinical re-isolates, based on the full VP1 sequence, suggest that vaccine-derived viruses may make
their way through narrow breaches and may evolve into transmissible pathogens even in adequately immunized populations. For
this reason increased poliovirus laboratory surveillance should be permanent and full VP1 sequence analysis should be conducted
even in isolates originating from healthy vaccinees. 相似文献
16.
Tuba Y. Yaln Deniz . Topu
zlem Doan Saliha Aydn Nuran Sar idem Erol Zeynep E. Kulolu
zlem K. Azap Füsun Can Hande Arslan 《Journal of medical virology》2022,94(1):279-286
Vaccines have been seen as the most important solution for ending the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the antibody levels after inactivated virus vaccination. We included 148 healthcare workers (74 with prior COVID-19 infection and 74 with not). They received two doses of inactivated virus vaccine (CoronaVac). Serum samples were prospectively collected three times (Days 0, 28, 56). We measured SARS-CoV-2 IgGsp antibodies quantitatively and neutralizing antibodies. After the first dose, antibody responses did not develop in 64.8% of the participants without prior COVID-19 infection. All participants had developed antibody responses after the second dose. We observed that IgGsp antibody titers elicited by a single vaccine dose in participants with prior COVID-19 infection were higher than after two doses of vaccine in participants without prior infection (geometric mean titer: 898 and 607 AU/ml). IgGsp antibodies, participants with prior COVID-19 infection had higher antibody levels as geometric mean titers at all time points (p < 0.001). We also found a positive correlation between IgGsp antibody titers and neutralizing capacity (rs = 0.697, p < 0.001). Although people without prior COVID-19 infection should complete their vaccination protocol, the adequacy of a single dose of vaccine is still in question for individuals with prior COVID-19. New methods are needed to measure the duration of protection of vaccines and their effectiveness against variants as the world is vaccinated. We believe quantitative IgGsp values may reflect the neutralization capacity of some vaccines. 相似文献
17.
Christian Goilav Jane Zuckerman Michael Lafrenz Emmanuel Vidor Sabine Lauwers Christine Ratheau Grazia Benichou Arie Zuckerman 《Journal of medical virology》1995,46(3):287-292
A multicentre, controlled, randomised, open, comparative trial including 839 healthy adult volunteers was carried out in order to compare the immunogenicity and reactogenicity of two vaccines against hepatitis A virus (HAV) during primary immunization and after booster injection. The first vaccine was produced by Pasteur Mérieux (PM), and the second vaccine by Smith-Kline Beecham (SKB). The vaccination schedule consisted of 2 doses (months 0, 6) for PM and 3 doses (months 0, 1, and 6) for SKB. Two weeks after the first dose, the seroconversion rates among initially HAV seronegative subjects (n = 608) were 93.4% and 76.1% for the PM and SKB vaccines, respectively, the corresponding geometric mean titres (GMTs) were 59.0 mlU/ml versus 30.8 mlU/ml (modified RIA HAVAB assay, Abbott Laboratories). Two months after the beginning of immunization (one dose versus two doses) the GMTs were 138.4 and 161.6 mlU/ml, respectively. At month 7, the seroconversion rates were 100% for both vaccines, and the GMTs were 4, 189 and 3, 163 mlU/ml, respectively. After the first dose of vaccine, 24.6% and 19.6% of the PM and SKB vaccinees reported local reactions. The rates for systemic reactions were 27.2% and 25.0%, respectively. Lower rates for local and systemic reactions were seen after booster injections and statistical differences were not observed between the two vaccines. The study also demonstrated that vaccination was as well tolerated in subjects with anti-HAV antibodies as in HAV seronegative subjects. Logistic regression analysis revealed a significant vaccine effect on seroconversion rates only at week 2 (P<10?4). The same conclusions were drawn from the analysis of GMT by multivariate regression. When both times (week 2 and week 8) were analysed together, a statistically significant effect of interaction between time and vaccine was observed, indicating that the kinetics of antibody responses were different. © 1995 Wiley-Liss, Inc. 相似文献