空斑减少中和试验测定血清抗乙脑病毒抗体

目的：对比空斑减少中和试验与反向被动血凝抑制试验在评价人血清抗乙脑病毒抗体时间定结果的异同。方法：对450名6－10岁儿童接种灭活乙脑疫苗前后的血清样本用两种方法进行了测定。结果：两种方法在测定免前人血清抗乙脑病毒抗体时存在显性差异，在测定免后人血清抗乙脑病毒抗体时两没有差异。结论：空斑减少中和试验比反向被动血凝抑制试验在测定人血清抗乙脑病毒抗性时灵敏。     

应用捕获-ELISA试验与HI试验检测麻疹初免成功率的对比分析

国内外多用血凝抑制试验(简称HI试验)检测血凝抑制抗体(HI抗体)是否阳转测定麻疹初免成功率。此方法需采集双份血清(有些家长不愿接受),而且需时较长(免后1个月左右才能检测)。因此我们探讨用捕获-ELIsA方法测定血清中麻疹特异性IgM抗体(简称SIgM)进行初免成功率检测。现将捕     

捕获-EIA法用于麻疹疫苗免疫效果监测的初步探讨

用捕获-EIA法和血凝抑制试验同时检测72名麻疹疫苗初免者的特异性IgM抗体和血凝抑制抗体。结果表明,72份免疫前及7份未免疫成功者血清,两种方法检测结果完全相符(均为阴性)。65名血凝抑制抗体阳转者,捕获-EIA法检测结果的符合率为83~100%。特异性IgM抗体水平和动态与接种的疫苗病毒量相关。由此,我们认为捕获-EIA法完全可用于麻疹疫苗初免后的效果监测。     

麻疹病毒疫苗株沪191和宁波麻疹病毒流行株血清交叉中和试验结果分析

目的分析麻疹病毒疫苗株[上海(沪)191,Shanghai191;S191]的免疫保护性,为探讨有效预防控制麻疹的措施提供参考。方法用微量中和试验测定不同人群血清对麻疹病毒疫苗株(S191)和浙江省宁波市麻疹病毒流行株(Ningbo2008-06)的中和抗体(Neutralizing Antibody,NA)水平。结果 S191株麻疹减毒活疫苗(Measles Attenuated Live Vaccine,MV)初次免疫(初免)血清,有MV免疫史麻疹患者急性期血清,麻疹患者恢复期血清,应急接种MV前、后血清,对疫苗株的NA几何平均滴度(Geometric MeanTiter,GMT)分别为1∶35.23、1∶4.16、1∶231.74、1∶37.81、1∶61.03;对麻疹病毒流行株的NAGMT分别1∶19.04、1∶2.21、1∶596.62、1∶32.25和1∶67.54。初免血清及有免疫史麻疹患者急性期血清,对疫苗株的NAGMT分别是流行株的1.85倍(t=2.537,P<0.05)和1.88倍(t=-2.696,P<0.05);麻疹患者恢复期血清对流行株的NAGMT是疫苗株的2.57倍(t=-3.054,P<0.05);而应急接种后血清中和疫苗株和流行株的NAGMT差异无统计学意义。小月龄婴儿血清随着月龄增长对疫苗株和流行株的NAGMT均下降,6月龄和8月龄婴儿对流行株的NAGMT分别为1∶2.60和1∶1.24。结论 S191株MV能中和宁波麻疹病毒流行株,只是中和能力略有下降;应急接种能显著增加麻疹NA水平;母传麻疹抗体6月龄后几乎无保护作用;有必要对现行MV免疫策略进行调整。     

反向间接血凝抑制试验测定麻疹抗体

目的建立采用反向间接血凝抑制试验测定麻疹抗体的方法,并与传统的血凝抑制方法进行比较。方法采用麻疹单克隆抗体致敏人“O”型红细胞的反向间接血凝抑制法,检测麻疹抗体。结果两种方法检测麻疹疫苗免疫后抗体阳转率均为100％（11／11）;52份免疫后血清RPHI的GMT为26．55,HI的GMT为39．08,经统计学处理两种方法未见显著性差异,并具有很好的平行关系。应用该方法对其他相关病毒抗原和抗体的检测,结果无交叉反应。结论该法有较好的实际应用价值。     

辽宁省麻疹病毒流行株血凝蛋白特性分析

目的 比较辽宁省麻疹病毒流行株（MVW）和目前使用的疫苗株血凝蛋白基因（H）核苷酸（nt)及氨基酸（aa)序列差别,研究其生物学和免疫学特性及其基因型区别。方法 MVW流行株和长-47疫苗株的H基因1-1800nt及1-600aa序列分析;麻疹病人及疫苗免疫后的血清与MVW株和长-47疫苗株做中和抗体测定。结果 表明MVW株基因型不同于其它国家以前报道的MVW株基因型及我省现有物长-47疫苗株,有18-28个aa差异;还表明MVW株具有重要生物学和免疫学活性的aa位点,除aa238-240位点有一个aa发生变异外,其余均与长-47疫苗株相同,另外麻疹病人恢复期血清和麻疹疫苗初次免疫儿童（初免）后1个月的血清抗长-47及MVW毒株的中和抗体几何平均滴度（GMT）差别无显著性,但是麻疹病人恢复期血清对这两毒株中和抗体滴度均明显高于初免儿童的中和抗体滴度。结论 辽宁省的MVW株与长-47疫苗株基因型不同,说明MVW株nt存在变异,但是具有生物学和免疫学活性的aa位点多数未发生改变,长-47疫苗株仍然能保护MVW的感染。     

不同人群血清对麻疹疫苗株与流行株的中和能力比较

目的探讨不同人群血清对麻疹流行株与疫苗株中和能力的差异。方法采集麻疹患者急性期与恢复期血清、麻疹疫苗免疫前后儿童血清以及流动人口血清，分别对疫苗株沪191与2005年麻疹流行株进行中和抗体（NT）滴度测定。同时，利用疫苗株、浙江省当地流行株制备动物免疫血清，与相应毒株进行交叉中和试验，测定各毒株之间抗原比。结果疫苗免疫后儿童血清对疫苗株的中和抗体几何平均滴度（GMT）为50.82，高于流行株MVi／ZJ／05／7（GMT值为27．35）1．86倍；患者恢复期血清对流行株的中和能力（GMT值为386．95）显著高于疫苗株（GMT值为151．83）；流动人口血清对流行株中和抗体GMT值均小于疫苗株，差异为2．22～4．17倍；MVi／ZJ／99／1、MVi／ZJ／04／1和MVi／ZJ／05／7与疫苗株间抗原比分别为4．28、5．24和5．66。此外，部分患者急性期血清对疫苗株存在低滴度的中和抗体，GMT值1：4左右。结论不同人群血清对麻疹疫苗株与流行株的中和能力的差异有统计学意义，低滴度的疫苗抗体不能有效保护个体免受麻疹流行毒株的侵袭，应加强麻疹病毒变异与疫苗效果的相关研究。     

西安市麻疹流行病原毒株和疫苗免疫因素研究

目的 确定引起西安市麻疹流行的病原毒株，探讨相关的疫苗免疫因素。方法 采集麻疹病人咽拭子标本分离病毒，用酚-氯仿抽提法提取病毒悬液中的RNA，逆转录-聚合酶链反应（RT—PCR）扩增N基因碳末端的450个核苷酸（bp）片段，对扩增产物进行序列测定和基因分型。用微量中和试验测定麻疹病人急性期和恢复期血清中和麻疹疫苗株和野毒株的中和抗体水平。结果 采集咽拭子标本13份，分离出麻疹病毒8株，分离率61．54％；8株麻疹病毒均为H1基因型H1a亚型。结论 H1基因型H1a亚型是引起西安市本次麻疹流行的病原病毒。此次麻疹流行不排除疫苗保护性下降因素和麻疹疫苗免疫工作中存在无效接种而造成的免疫空白。     

陕西省麻疹病毒基因分型及疫苗免疫因素分析

目的确定引起陕西省麻疹流行的病原毒株,探讨相关的疫苗免疫因素。方法采集麻疹病人咽拭子标本分离病毒,用酚-氯仿抽提法提取病毒悬液中的RNA,逆转录-聚合酶链反应（RT-PCR）扩增N基因碳末端的核苷酸450个（bp）片段,对扩增产物进行序列测定和基因分型。用微量中和试验测定健康人群麻疹病人急性期血清中和麻疹疫苗株和野毒株的中和抗体水平。结果从82份咽拭子中分离出19株H1基因型麻疹病毒。麻疹疫苗免疫血清和有免疫史麻疹急性期病人血清对麻疹野毒株的中和抗体几何平均滴度（GMT）分别为26.36和26.90,明显低于疫苗株,GMT分别为49.30和56.18。结论陕西省近年麻疹流行是由H1基因型麻疹野病毒引起,不排除疫苗对目前流行株保护性不足的因素。     

麻疹病毒抗原性变异及免疫保护效果研究

目的 了解浙江省麻疹野毒株的抗原性变异状况以及麻疹疫苗的免疫保护效果。方法 采用麻疹国际标准株Edmonston株、疫苗株沪19l与近几年浙江省分离的麻疹野毒株(浙98-5和浙00-4)分别制备免疫血清，与各毒株进行交叉中和试验，并分别对不同来源的人群血清测定中和抗体滴度。结果 麻疹野毒株浙98-5与疫苗株沪川和Edm株的抗原比分别为3．0和2．6，浙00-4与上述两毒株的抗原比分别为7．30和5．65，其抗原性存在着明显的差异。麻疹疫苗初免儿童和麻疹急性期病人血清对麻疹野毒株的中和抗体几何平均滴度(GMT)分别为15．03和5．04，明显低于疫苗株沪19l，GMT分别为68．12和11．76。但健康人群血清对两毒株的中和抗体滴度无显性差异。结论 浙江省麻疹野毒株已出现较明显的抗原性变异，现行麻疹疫苗的免疫保护效果也受到一定影响。     

Waning of measles maternal antibody in infants in measles elimination settings – A systematic literature review

IntroductionMost infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination.MethodsWe conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool.ResultsWe identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3–7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune.ConclusionAlthough limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.     

Present anti-measles immunity in Jordan.

The immunity of adults and the prevalence of measles was determined in order to evaluate the adequacy of current measles vaccination policy in Jordan. A total of 307 sera, collected from adults aged 18--40 years, were tested for anti-measles antibodies by ELISA technique. The overall prevalence of anti-measles antibodies was 94.8% and there was no significant difference in the seropositivity rate between males (95.7%) and females (94%). Of the tested adults, 71% were vaccinated and 29% escaped vaccination. In Jordan, measles outbreaks occur periodically and predominantly attack children aged 5--14 years. Our data support introducing the compulsory MMR vaccine in the year 2000 to improve the vaccination coverage of measles; since the optional single dose vaccination has not interrupted the circulation of the measles virus. A second dose of MMR vaccine could be offered to Jordanians either at school entry or at the age of 11--12 years, based on the outcome of the compulsory single dose of MMR vaccine.     

Head-to-head immunogenicity comparison of Edmonston-Zagreb vs. AIK-C measles vaccine strains in infants aged 8–12 months: A randomized clinical trial

BackgroundA non-inferiority multi-centre parallel randomized double-blind trial was implemented in Zahedan district, Sistan-va-Baluchestan province, Iran, to compare the performance of the two measles vaccines which are in use in the National Immunization Programme of Iran and are of two different measles virus vaccine strains: Edmonston-Zagreb (EZ) strain vs. AIK-C strain. The main outcome measure was appearance of anti-measles antibody in sera.Methods200 infants, 8–12 months old, whose parents consented for their children to be included in the study, were randomized in permutation blocks of size 4–8 in four Urban Health Clinics. Having given a pre-vaccination blood sample, they received measles-rubella vaccine containing one of the vaccine strains mentioned before. After 60 days, the second blood sample was taken. The sera of the pre- and post-vaccination blood samples were tested for anti-measles antibodies in the National Reference Measles Laboratory. Parents, laboratory technicians and statistician were blind to groupings.ResultsOf the 200 children equally randomized in the two arms, 185 who were seronegative before vaccination (88 in the EZ arm and 97 in the AIK-C arm) were entered in the final analysis. The seroconversion rate in the EZ arm was 76.1% (95% CI: 60.2–85.2%), and that in the AIK-C arm was 58.7%; (95% CI: 48.8–68.7%). The absolute rate difference was 17. 4% (4.1–30.9%; P-value: .012), and the relative seroconversion rate of EZ to AIK-C was 1.3 (95% CI: 1.1–1.6; P-value: .012). No adverse events were reported during the study period.ConclusionA considerable difference in the seropositivity of different measles containing vaccines could be demonstrated in the first year of life.Trial Registration: Iranian Registry of Clinical Trials Registration Number: IRCT2016032827144N1; May 10, 2016 (www.who.int/ictrp/network/irct/en/)     

Seroprevalence of anti-rubella and anti-measles antibodies in women at the verge of marriage in Iran

BackgroundMeasles and rubella as two highly contagious eruptive diseases are on the agenda to be eliminated in Iran by 2020. To evaluate the seroimmunity of the future mothers against rubella and measles, a nationwide serosurvey was implemented in 10 provinces, selected at random from 31 provinces in the country.Methodsusing a multistage sampling method, 1600 participants were interviewed and blood sampled in 40 'Pre-marriage Consultation Centers' across 40 districts. Using ELISA method, the sera were tested for anti-rubella and anti-measles IgG antibodies in the National Reference Laboratory for Measles and Rubella, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.ResultsOf the 1600 initial participants, the sera of 1573 participants were tested for rubella and 1569 for measles. The total seroprevalence of anti-rubella and anti-measles antibodies were 90.6% (95%CI: 89.1 to 92.0%) and 80.7% (95%CI: 78.7 to 82.6%) respectively. After 14 years, the effect of the immunization campaign of 2003 against rubella and measles on the age group of 5 to 25 years, was still apparent, i.e., there was a sharp difference between the seroprevalence of antibody (against both measles and rubella) of those who at the time of the present study were above 18 years with the younger age cohorts. For both diseases, higher seroprevalence of antibodies was detected in women above 18 years old.ConclusionImplementation of a Supplemental Immunization activity or revision of the national immunization schedule to add a third dose of measles and rubella containing vaccine during adolescence are/might be considered as possible options for bridging the gap in the seroimmunity of the younger age groups.     

Evaluation of the effect of maternally derived antibody on response to MMR vaccine in Thai infants

BackgroundAlthough the number of measles cases declined globally in response to anti-measles immunisation campaigns, measles has re-emerged. A review of current vaccination policies is required to improve measles elimination strategies.MethodsA pseudotype-based virus neutralisation assay (PVNA) was used to measure neutralising antibody titres in serum samples collected from Thai infants at six timepoints before and after two-doses of MMR (1&2) vaccination (ClinicalTrials.gov no. NCT02408926). Vesicular stomatitis virus (VSV) luciferase pseudotypes bearing the haemaglutinin (H) and fusion (F) glycoproteins of measles virus (MeV) were prepared. Serial dilutions of serum samples were incubated with VSV (MeV) pseudotypes and plated onto HEK293-human SLAM1 cells; the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity.ResultsNeutralising antibody titres in infants born with high levels of maternal immunity (H group) persisted at the time of the first MMR vaccination, and those infants did not respond effectively by developing protective titres. In contrast, infants with lower maternal immunity (L group) developed protective titres of antibody following vaccination. Responses to the second MMR vaccination were significantly higher (P = 0.0171, Wilcoxon signed-rank test) in the H group. The observed correlation between anti-MeV IgG level and neutralising antibody titre in Thai infants indicates the possibility of using rapid IgG testing as a surrogate measure for neutralising activity to define clinical protection levels within populations.ConclusionThese results demonstrate that varying the timing of the first MMR immunisation according to the level of acquired maternal immunity could increase vaccination immunogenicity and hence accelerate measles eradication.     

母体麻疹抗体与婴儿麻疹发病关系的研究

目的探讨母体麻疹抗体与婴儿麻疹发病关系,为降低婴儿麻疹发病,提供科学依据。方法对枣庄市1999-2011年婴儿麻疹发病状况及采用酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)对母体、婴儿、育龄妇女麻疹抗体调查分析。采用SPSS 11.5软件统计分析,分析方法采用χ2检验、t检验、F检验,以P<0.05为差异有统计学意义。结果 1999-2011年共发生麻疹1 485例,婴儿占38.45%;其中<8月龄占23.10%。2004年前(1999-2004年)后(2005-2011年),<8月龄婴儿麻疹所占比例分别为4.46%和30.59%;婴儿平均发病月龄分别为9.38月和7.65月,差异均有统计学意义(χ2=23.62、t=2.74,P均<0.01)。育龄妇女麻疹几何平均倒数滴度(GMRT)2001年最高,为675.50,2009年最低,为370.23;各年份间差异有统计学意义(F=10.78,P<0.01)。婴儿麻疹抗体阳性率、GMRT,2005和2009年6月龄与1999年8月龄相当,差异均无统计学意义(χ2=0.36、t=1.21,P均>0.05)。婴儿患与未患麻疹,其母体抗体阳性率、GMRT分别为79.88%,373.63;86.48%,510.85,差异均有统计学意义(χ2=5.44,P<0.05;t=4.21,P均<0.01)。结论母体麻疹抗体与婴儿麻疹密切相关,随母传麻疹抗体的提前消失婴儿发病月龄趋于前移。因此,提高母体麻疹抗体水平,是控制婴儿麻疹的根本措施。     

Safety and immunogenicity of live-attenuated Japanese encephalitis SA 14-14-2 vaccine co-administered with measles vaccine in 9-month-old infants in Sri Lanka

Introduction

To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine at 9 months of age. Serum immune responses were evaluated post-vaccination on days 28, 180, and 365 using JE neutralization test and anti-measles IgG ELISA.

Results

278 infants received one dose of LJEV and measles vaccine. Of these, 257 were eligible for the per-protocol analysis. On Day 0, 14 infants (5.5%) were seropositive for JE, but none were seropositive for measles. At Day 28, seropositivity rates were 90.7% (95% CI, 86.4–93.9%) for JE and 84.8% (95% CI, 79.8–89.0%) for measles. The geometric mean titer for JE neutralizing antibodies was 111 (95% CI, 90–135), and the geometric mean concentration (GMC) for anti-measles IgG was 375 mIU/mL (95% CI, 351–400 mIU/mL). Over the next year, JE neutralizing antibody responses declined only slightly, with seropositivity at 87.4% (95% CI, 82.6–91.2%) at Day 365. In contrast, measles antibody levels continued to increase over time. Seropositivity for anti-measles IgG reached 97.2% (95% CI, 94.4–98.9%) at Day 365, and the GMC rose to 1202 mIU/mL (95% CI, 1077–1341 mIU/mL). Co-administration of LJEV and measles vaccine was also safe. Most adverse reactions were mild, and no serious adverse events were related to study vaccinations.

Conclusion

The safety and immunogenicity of LJEV co-administered with measles vaccine in Sri Lankan infants is similar to that seen in other populations, and our results support use of LJEV at 9 months of age. Live SA 14-14-2 vaccine is now prequalified by the WHO for use in infants in Asia, and other countries may wish to introduce LJEV to combat this devastating disease.     

Antibody against viruses in maternal and cord sera: specific antibody is concentrated on the fetal side of the circulation.

Paired maternal and cord sera from 100 pregnancies were tested for antibodies against herpes simplex virus, measles virus and respiratory syncytial virus by complement fixation and for antibodies against rubella virus, influenza A virus and influenza B virus by haemagglutination-inhibition. For four viruses (herpes simplex, measles, respiratory syncytial and rubella) higher levels of antibody were found in cord than in maternal sera. There was no difference between maternal and cord serum titres against influenza B virus but significantly higher levels of antibody against influenza A virus were found in maternal sera than in cord sera. This discrepancy was investigated by measuring antibodies against the surface antigens of influenza A by a complement fixation technique, and by single radial haemolysis. Both methods showed a preponderance of virus-specific antibody in cord sera. We conclude that IgG antibodies against most, if not all, viruses are concentrated on the fetal side of the circulation, but the conventional haemagglutination-inhibition techniques may fail to detect this difference.     

麻疹野病毒的分离及血清学的初步分析

从１９９３年山东省和湖南省１０例麻疹急性期患者的咽拭子中，用Ｂ９５ａ细胞分离到７株麻疹野病毒，同时用 Ｖｅｒｏ细胞分离未获成功。将此 ７株病毒以 １０４ＴＣＩＤ５０／ｍｌ剂量分别接种到 Ａ－Ｖｅｒｏ细胞，只有１株出现融合病变，其它毒株未见增殖。抗麻疹血凝素（Ｈ蛋白）单克隆抗体（１２Ｅ）对分离株的中和滴度低于Ｌ４株６０倍以上。在同期收集的１３例麻疹患者血清，经ＥＬＩＳＡ法检测，３ 例ＩｇＧ抗体阴性，３例抗体滴度为１：２００～１：８００，但７例滴度在１：３２００～１：１０２　４００之间，占５４％．１３例血清中１２例ＩｇＭ抗体阳性。