水痘疫苗及其免疫策略

水痘是由水痘-带状疱疹病毒(VZV)引起的儿童期高度传染性疾病。世界各地都有发生。VZV初次感染后可在体内建立潜伏感染,以后可被激活引起带状疱疹。1974年研制成功的水痘减毒活疫苗对预防和控制水痘有着重要作用。该文介绍了水痘疫苗的由来、安全性、免疫效果和免疫策略等。     

人群中水痘-带状疱疹病毒流行率及其疫苗免疫效果

为了解健康人群水痘－带状疱疹病毒（VZV）流行情况及国产Oka株水痘减毒活疫苗（水痘疫苗）的免疫效果，采用酶联免疫吸附试验（ELISA）监测了384名0～50岁健康人群VZV的血清流行病学情况，同时对国产水痘疫苗在2～6岁无水痘感染史及疫苗接种史的健康儿童中进行了免疫原性和人体反应性观察。结果显示人群中血清抗VZV－IgG阳性率平均为64.32％，年龄别流行率在0～2岁、3～6岁、7～12岁、13～19岁和40～50岁组分别为13.24％、29.58％、75.71％、88.57％和100.00％。说明血清年龄别流行率以0～2岁组最低，以后随年龄增长而很快上升。国产水痘疫苗接种后全身和局部反应轻微，血清抗体阳转率为94.1％，几何平均滴度为18.400。证明了该疫苗有良好的有效性和安全性，可用作水痘－带状疱疹病毒自动免疫预防。     

儿童水痘血清流行率调查及其疫苗免疫效果

为了解儿童水痘流行情况及水痘减毒活疫苗的免疫效果 ,采用全抗原ELISA方法对 315名3～ 7岁儿童水痘的血清流行情况进行了调查 ,血清抗VZV -IgG阳性率为 4 1.6% ,且不同幼儿园中水痘流行情况有所不同 ,表现出明显的群体差异。同时对Oka株水痘减毒活疫苗在该人群的免疫效果进行了调查 ,结果表明该疫苗接种后无明显副反应 ,血清阳转率为 85.1%。证明了减毒活疫苗有良好的安全性和有效性。     

某幼儿园水痘暴发事件调查和疫苗保护效果研究

目的调查水痘暴发事件，了解水痘疫苗保护效果，为制定科学防控策略和措施提供依据。 方法搜索2018年9月1日至2019年1月23日，该幼儿园儿童和教职员工中出现典型的水痘样皮疹(丘疹或疱疹或结痂)者。采集8例患者的咽拭子标本开展病原学检测；利用"问卷星"和"江苏省预防接种综合服务管理信息系统"平台，收集6个班级的所有儿童的水痘疫苗接种等信息，调查疫苗的保护效果。 结果共搜索到水痘患者106例，儿童罹患率为14.5%(104/717)，教职工罹患率为2.8%(2/72)；首例患者为小6班儿童，2018年9月6日发病，疫情持续4个月，流行曲线显示为增殖模式，患者可分为8代。暴发波及8个班级，班级罹患率17.5%～58.5%；接种水痘疫苗者中的水痘罹患率为12.9%(8/62)，未接种水痘疫苗者中水痘罹患率为54.4%(81/149)，水痘疫苗保护率为76%(95%CI＝54%～88%)；37.5%(3/8)患者咽拭子标本水痘-带状疱疹病毒核酸阳性。 结论在低免疫水平人群中暴发水痘的防控难度大，水痘疫苗保护效果较好，建议进一步加强水痘疫苗接种宣传，将儿童水痘疫苗接种纳入扩大免疫规划。     

国产与进口水痘减毒活疫苗安全性和免疫效果Meta分析

比较国产与进口水痘疫苗在中国人群中的安全性和免疫效果,为探讨适用于中国人群的疫苗提供循证医学依据.方法 以“水痘”(varicella or chickenpox)、“水痘减毒活疫苗”(varicella or chickenpex attenuated live vaccine)、“安全性”(safety)、“免疫效果”(immunogenicity)为关键词,检索1998-2013年公开发表的、符合入选标准的有关水痘疫苗的中英文研究文献,进行Meta分析.结果 有12篇文献纳入研究,其中水痘减毒活疫苗(VarV)实验性研究9篇(随机对照试验4篇),病例对照研究3篇.国产与进口VarV局部不良反应RR合并=0.45,95%CI为0.28~0.70(P<0.05);全身不良反应RR合并=1.45,95% CI为0.58~3.65(P>0.05);抗体阳转率RRA并=1.00,95% CI为0.97~1.02(P>0.05);疫苗保护效果OR合并=1.03,95%CI为0.52~2.03(P>0.05).结论 国产VarV在中国人群中的安全性和免疫效果良好,与进口VarV差异无统计学意义.     

国产冻干水痘减毒活疫苗免疫效果观察

目的：观察国产冻干水痘减毒活疫苗的免疫效果。方法：在广西桂林市漳阳县和吉林省和龙市选择1—6岁健康易感儿童接种国产冻干水痘减毒活疫苗，进行安全性、免疫原性观察；同时，选择与疫苗接种密切接触的非接种进行疫苗株传播性观察。结果：410名观察对象接种水痘疫苗后无明显副反应。检测有效血清271份，血清抗体阳转率为98．89％，GMT为1:36.83％。该疫苗株接种不存在传播性。结论：接种国产冻干水痘减毒活疫苗安全、有效。     

水痘疫苗及其免疫策略

目的分析上海市长宁区适龄儿童在接种1剂水痘疫苗1年后,再次接种1剂国产水痘减毒活疫苗(水痘疫苗)的血清抗体水平变化情况。方法以长宁区曾经接种过1剂水痘疫苗的1~3岁儿童为观察对象,共计入组206人。间隔1年对观察对象接种第2剂次水痘疫苗,于接种疫苗前和接种后35~42 d采集静脉血,用膜免疫荧光法(FAMA)进行血清水痘抗体水平检测,比较第2剂水痘疫苗接种前后抗体水平的差异。结果比较观察对象在接种第2剂水痘疫苗前后的血清水痘抗体滴度情况,免前的抗体几何平均滴度(GMT)为1:11.90,免后的GMT为1:71.04,后者的抗体水平明显高于前者,差异有统计学意义(t=18.1,P＜0.01)。抗体增长≥4倍者比例为82.52%。结论间隔1年后接种第2剂水痘疫苗能有效提高受种者血液中的水痘抗体滴度。     

我国部分地区人群中水痘-带状疱疹病毒流行率

本文首次报导我国部分城市居民中水痘－带状疱疹病毒（Ｖａｒｉｃｅｌａ－ｚｏｓｔｅｒｖｉｒｕｓ，ＶＺＶ）血清学流行率。标本来自上海、北京、大连、广州和成都市１～４５岁人群，共收集血清３０７６人份。用ＥＬＩＳＡ方法检测。结果显示，我国部分人群中ＶＺＶ抗体阳性率平均为６８７６％，年龄别流行率在１～３岁、４～６岁、７～１３岁和３６～４５岁组，分别为１５９６％、４９９０％、６９９４％和９３１２％。此结果将为我国ＶＺＶ疫苗免疫中免疫对象的选择提供科学依据     

福建省健康人群水痘——带状疱疹病毒血清流行病学调查

目的 为了解健康人群中水痘——带状疱疹病毒(VZV)流行情况。方法 采用ELISA法对福州市371名健康人群血清标本进行血清学监测。结果 1～岁、4～岁、7～岁、13～岁、19～岁、30～岁，40～49岁年龄别流行率分别为13．8％，33．9％，70．9％，87．3％，94．1％，95．8％，97．9％。血清学流行率以1～3岁组最低，以后随年龄增长而上升。结论 水痘病毒在人群中的感染率很高，6岁以下婴幼儿应是水痘疫苗免疫的首选对象。     

水痘疫苗不同免疫策略实施与控制效果研究进展

水痘是一种疫苗可预防的具有高度传染性的儿童期常见病。近年来,越来越多的国家通过使用水痘疫苗实现对疾病的防控。本文对国内外不同国家的水痘疫苗免疫策略实施进展、控制效果以及对带状疱疹流行特征的影响进行综述,以期能全面的认识水痘疫苗不同免疫策略在疾病预防、控制以及人群流行特征变化等方面所起的作用。     

国产水痘减毒活疫苗接种的血清学免疫效果及成本效益分析

[目的 ]　观察不同代次、不同剂量的国产水痘减毒活疫苗的安全性和免疫效果 ,分析不同年龄组儿童水痘疫苗接种的经济效益。　 [方法 ]　随机分组 ,接种不同代次、不同剂量的国产水痘疫苗 ,对每组儿童进行人体反应性及免疫原性观察 ,用酶联免疫吸附法 (ELISA)测定水痘抗体 ,采用成本效益分析方法计算各年龄组效益费用比 (BCR)。　 [结果 ]　各组水痘疫苗免后副反应率及抗体水平差异均无显著性。免后 1～ 3月 ,抗体阳转率达到 96 %以上 ,几何平均滴度(GMT)达到 76 0以上。以后抗体逐渐下降 ,接种后 2年抗体阳转率为 81.40 %,GMT为 36 7.2 0。水痘疫苗接种后成本效益比值 ,2岁以下年龄组BCR值小于 1,3～ 7岁年龄组BCR值均大于 1,其中 6～ 7岁组经济效益最高。　 [结论 ]　不同代次、不同剂量的国产水痘疫苗副反应率较低 ,免疫效果好。 3～ 7岁组儿童接种水痘疫苗能获得正效益 ,应作为水痘疫苗免疫接种的首选对象。     

The immunopotentiator CVC1302 enhances immune efficacy and protective ability of foot-and-mouth disease virus vaccine in pigs

The immunological enhancement characteristics of the immunopotentiator CVC1302 were evaluated for foot-and-mouth disease virus (FMDV) inactivated vaccine in pigs. Eight-week-old piglets were vaccinated with the foot-and-mouth disease (FMD) vaccine alone (FMD-vaccine group) or with the addition of CVC1302 (FMD-CVC1302 group), and the serum liquid phase blocking ELISA (LPB-ELISA) antibody titers, IgG1 and IgG2 levels, and the levels of four cytokines secreted by peripheral blood lymphocytes were measured at 28 days post vaccination (dpv). In the FMD-CVC1302 group, the LPB-ELISA antibody titers, IgG1, and IgG2 titers, and IL-2, IL-4, IL-6, and IFN-γ levels at 28 dpv were significantly higher than those in the FMD-vaccine group. The FMD-CVC1302 group had long-lasting antibody titers (>7.8 log₂), lasting for at least 6 months. In addition, piglets were vaccinated with or without addition of CVC1302 to the FMD vaccine at three different doses (1, 1/3, and 1/9 of the standard vaccine dose) and the serum LPB-ELISA antibody and serum neutralizing (SN) antibody titers were detected at 28 dpv. Then all pigs were challenged with virulent FMDV for PD₅₀ value, and the levels of FMDV-specific RNA copies for the two full-dose groups at 3 and 10 days post challenge (dpc) were measured. The LPB-ELISA and SN antibody titers for the three doses in the FMD-CVC1302 groups were significantly higher than those in the FMD-vaccine groups at the same doses (p < 0.05). Post-virus challenge, the FMDV-specific RNA copy number in the FMD-CVC1302 group was lower than that in the FMD-vaccine group at 3 and 10 dpc. The PD₅₀ value was 15.85 for the FMD-CVC1302 group, which was obviously higher than that for the FMD-vaccine group (10.96), and in the 1/9-dose of FMD-vaccine group only 3/5 pigs were protected. These results indicate that CVC1302 can enhance the immune efficacy and protective ability of the FMD vaccine in pigs.     

水痘疫苗接种儿童水痘IgG水平的横断面研究

[目的] 观察儿童1剂水痘疫苗（VarV）免疫的持续效果及其影响因素,初探加强免疫方案。[方法] 采集≤12岁接种1剂水痘疫苗的健康儿童手指末梢血629份,用定量酶联免疫吸附试验（ELISA）测定水痘IgG水平,同时调查VarV记录和水痘患病史。[结果] 儿童水痘IgG浓度值呈偏态分布,P₂₅为40.19 mIU/mL,P₅₀为96.42 mIU/mL,P₇₅为290.82 mIU/mL,抗体对数值为（2.02±0.69） mIU/mL（95%CI：1.97～2.07）。不同接种年限和不同年龄组抗体浓度值差异有统计学意义（F=2.723,P=0.006和F=3.933,P=0.002）。儿童水痘IgG阳性率为69.0%,本地儿童抗体阳性率显著高于外来儿童（χ²=3.934,P=0.047）。抗体阳性率按VarV接种年限呈U形分布,拐点在接种后4年。[结论] 水痘疫苗接种后4年IgG浓度值降到低点,易受水痘感染。建议儿童在接种第一剂满3年后,加强1剂VarV免疫以获更有效免疫保护。     

Use of a current varicella vaccine as a live polyvalent vaccine vector

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The varicella vaccine was developed to control VZV infection in children. The currently available Oka vaccine strain is the only live varicella vaccine approved by the World Health Organization. We previously cloned the complete genome of the Oka vaccine strain into a bacterial artificial chromosome vector and then successfully reconstituted the virus. We then used this system to generate a recombinant Oka vaccine virus expressing mumps virus gene(s). The new recombinant vaccine may be an effective polyvalent live vaccine that provides protection against both varicella and mumps viruses. In this review, we discussed about possibility of polyvalent live vaccine(s) using varicella vaccine based on our recent studies.     

Review of the United States universal varicella vaccination program: Herpes zoster incidence rates,cost-effectiveness,and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data

In a cooperative agreement starting January 1995, prior to the FDA's licensure of the varicella vaccine on March 17, the Centers for Disease Control and Prevention (CDC) funded the Los Angeles Department of Health Services’ Antelope Valley Varicella Active Surveillance Project (AV-VASP). Since only varicella case reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in 2000 at which time approximately 50% of children under 10 years of age had been vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002, notable increases in HZ incidence rates were reported among both children and adults with a prior history of natural varicella. However, CDC authorities still claimed that no increase in HZ had occurred in any US surveillance site. The basic assumptions inherent to the varicella cost–benefit analysis ignored the significance of exogenous boosting caused by those shedding wild-type VZV. Also ignored was the morbidity associated with even rare serious events following varicella vaccination as well as the morbidity from increasing cases of HZ among adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of vaccinees were experiencing breakthrough varicella and vaccine-induced protection was waning, the CDC recommended a booster dose for children and, in 2007, a shingles vaccination was approved for adults aged 60 years and older. In the prelicensure era, 95% of adults experienced natural chickenpox (usually as children)—these cases were usually benign and resulted in long-term immunity. Varicella vaccination is less effective than the natural immunity that existed in prevaccine communities. Universal varicella vaccination has not proven to be cost-effective as increased HZ morbidity has disproportionately offset cost savings associated with reductions in varicella disease. Universal varicella vaccination has failed to provide long-term protection from VZV disease.     

水痘减毒活疫苗现场流行病学保护效力的Meta分析

目的 评价水痘减毒活疫苗现场流行病学保护效力,为优化水痘减毒活疫苗免疫程序提供依据.方法 电子检索《中国期刊全文数据库》和《美国国家医学图书馆数据库》,采用Meta分析对2000年以来发表的水痘减毒活疫苗保护效力病例对照研究的文献进行汇总、归纳和统计分析.使用RevMan5.1软件进行统计分析.结果 共纳入24篇文献.水痘减毒活疫苗总保护效力为69％ (95 ％CI:60％～75％),对幼儿(＜7岁)保护效力为86％ (95％CI:75％～92％),对小学生(≥7岁)的保护效力为67％(95％CI:50％～79％).结论 水痘减毒活疫苗具有一定的保护效力,但随着时间的推移保护效果降低.     

Susceptibility of Oka varicella vaccine strain to antiviral drugs

Susceptibility of Oka varicella vaccine virus to antiherpetic drugs was determined by the effective dose for 50% plaque reduction (ED₅₀) using cell-free virus preparation. ED₅₀ values were 3.02 μ for acyclovir, 3.72 μ for vidarabine, 0.0035 μ for sorivudine, and 4.67 μ for penciclovir. Oka varicella vaccine virus was as susceptible to these drugs as wild-type viruses. Sensitivity of thymidine kinase (TK)-deficient virus to penciclovir and of some DNA polymerase (DPase) mutants to sorivudine suggested that these drugs might be used for the treatment of vaccine recipients, even if Oka varicella vaccine became acyclovir-resistant by mutations in the TK or DPase genes, respectively. This result encourages the wider use of Oka varicella vaccine even for immunocompromised hosts because of its attenuation and susceptibility to chemotherapeutic drugs.     

Responses of varicella zoster virus (VZV)-specific immunity in seropositive adults after inhalation of inactivated or live attenuated varicella vaccine

To examine boostering of varicella zoster virus (VZV)-specific immunity in seropositive adults after nasal inhalation of heat-inactivated or live attenuated varicella vaccine, we determined specific cellular immunity, IgG antibody in sera and secretory IgA antibody in saliva before and after the inhalation. The mean titers in specific IgG antibody and skin test findings significantly increased following inhalation of both vaccines. However, the ratio of a two-fold or more increase in the levels of IgG antibody or skin test did not show significant difference after inhalation of the inactivated vaccine in comparison with those in the control. After inhalation of the live vaccine, the ratio showed significant difference but transmission of the live vaccine virus to others was suspected. No significant increase in VZV-secretory IgA antibody levels in saliva was noted following inhalation. The results of this study suggested that nasal inhalation of the live vaccine could increase specific immunity in adults. This method would be similar to the natural infection and simpler than subcutaneous injection.     

Safety surveillance of varicella vaccine using tree-temporal scan analysis

ImportancePassive surveillance systems are susceptible to the under-reporting of adverse events (AE) and a lack of information pertaining to vaccinated populations. Conventional active surveillance focuses on predefined AEs. Advanced data mining tools could be used to identify unusual clusters of potential AEs after vaccination.ObjectiveTo assess the feasibility of a novel tree-based statistical approach to the identification of AE clustering following the implementation of a varicella vaccination program among one-year-olds.Setting and participantsThis nationwide safety surveillance was based on data from the Taiwan National Health Insurance database and National Immunization Information System for the period 2004 through 2014. The study population was children aged 12–35 months who received the varicella vaccine.ExposureFirst-dose varicella vaccine.Outcomes and measuresAll incident ICD-9-CM diagnoses (emergency or inpatient departments) occurring 1–56 days after the varicella vaccination were classified within a hierarchical system of diagnosis categories using Multi-Level Clinical Classifications Software. A self-controlled tree-temporal data mining tool was then used to explore the incidence of AE clustering with a variety of potential risk intervals. The comparison interval consisted of days in the 56-day follow-up period that fell outside the risk interval.ResultsAmong 1,194,189 varicella vaccinees with no other same-day vaccinations, nine diagnoses with clustering features were categorized into four safety signals: fever on days 1–6 (attributable risk [AR] 38.5 per 100,000, p < 0.001), gastritis and duodenitis on days 1–2 (AR 5.9 per 100,000, p < 0.001), acute upper respiratory infection on days 1–5 (AR 11.0 per 100,000, p = 0.006), and varicella infection on days 1–9 (AR 2.7 per 100,000, p < 0.001). These safety profiles and their corresponding risk intervals have been identified in previous safety surveillance studies.ConclusionsUnexpected clusters of AEs were not detected after the mass administration of childhood varicella vaccines in Taiwan. The tree-temporal statistical method is a feasible approach to the safety surveillance of vaccines in populations of young children.     

The combination of Pleurotus ferulae water extract and CpG-ODN enhances the immune responses and antitumor efficacy of HPV peptides pulsed dendritic cell-based vaccine

Our previous study reported that the combination of Pleurotus ferulae water extract (PFWE) and CpG (PFWE + CpG) enhanced the maturation and function of dendritic cells (DCs). Here, we investigated the effects of PFWE + CpG on the immune responses and antitumor efficacy of DC-based vaccine. We observed that all of HPV E6 and E7 peptides pulsed DCs (HPV-immature DCs, HPV + PFWE-, +CpG- or +PFWE + CpG-DCs) induced antigen-specific CD8⁺ T cell responses and HPV + PFWE + CpG-DCs induced highest level of CD8⁺ T cell responses. The antitumor efficacy of HPV-DCs vaccines was evaluated in TC-1 tumor mouse model. The early therapeutic study showed that HPV + PFWE-, +CpG- and +PFWE + CpG-DCs greatly inhibited tumor growth. Moreover, HPV + PFWE + CpG-DCs controlled tumor growth at a faster rate compared to other groups. These three groups induced HPV-specific CD8⁺ T cell responses and significantly decreased the frequencies of induced regulatory T cells (iTregs: CD4⁺CD25⁻Fopx3⁺). However, only HPV + PFWE + CpG-DCs significantly decreased the frequency of natural Tregs (nTregs: CD4⁺CD25⁺Fopx3⁺). Furthermore, HPV + PFWE + CpG-DCs also significantly inhibited tumor growth in the late therapeutic study. The results showed that PFWE + CpG enhanced the immune responses and antitumor efficacy of DC-based vaccine, suggesting that PFWE + CpG might be the potential candidate for the generation of clinical-grade mature DCs.