甲型肝炎减毒活疫苗保护效果的Meta分析

目的 评价甲型肝炎减毒活疫苗(甲肝活疫苗;Attenuated Live Hepatitis A Vaccine)的保护效果.方法 电子检索MEDLINE、EMBASE、<中国期刊全文数据库>(CNKI)和<万方全文数据库>等数据库,将甲肝活疫苗保护效果研究的随机对照试验和半随机对照试验纳入分析,由2名评价员共同提取资料并评价纳入研究质量.用Revman 4.2软件进行统计分析.结果 共纳入13篇文献.所有研究均采用了随机方法,但大多数研究是半随机对照试验,2个研究遵循了盲法原则,所有研究都未采用分配隐藏.H2株与L-A-1株甲肝活疫苗都有很好的保护效果,疫苗保护效果与疫苗滴度密切相关,滴度<105.5 TCID50的甲肝活疫苗保护率为79%[95%可信区间(CI)为71%～85%],滴度≥106.5TCID50的甲肝活疫苗保护率为96%(95%CI为93%～98%).结论 甲肝活疫苗有良好的保护效果,滴度≥106.5 TCID50 的甲肝活疫苗的保护效果同甲肝灭活疫苗的保护效果基本一致.     

深圳市宝安区2007-2013年出生儿童接种1剂次水痘减毒活疫苗的保护效果评价

目的 评价深圳市宝安区2007-2013年出生儿童接种1剂次水痘减毒活疫苗的保护效果。 方法 获取深圳市宝安区2008-2016年水痘发病情况,选取其中2007-2013年出生儿童,其水痘免疫史从《深圳市免疫规划信息管理系统》中导出。计算水痘发病率、水痘疫苗接种率及疫苗保护效果。 结果 深圳市宝安区2007-2013年出生儿童水痘病例5 575例,突破病例833例,占14.94%。2007-2013年各年出生儿童水痘疫苗接种率逐年上升,随着水痘疫苗接种率升高,发病率下降,两者呈负相关(r=-0.963,P=0.000)。对2007年出生儿童接种1剂水痘疫苗的保护效果进行估算,总VE为74.42%(95%CI:71.30%~78.50%);接种后≤3年、接种4~5年、≥6年的VE分别为95.40%(95%CI:93.40%~96.70%)、90.80%(95%CI:88.30%~92.90%)、81.61%(95%CI:77.90%~84.60%),随着免疫后时间的延长,VE呈下降趋势(χ²_趋势=62.889,P=0.000)。 结论 深圳市宝安区2007-2013年出生儿童接种1剂次水痘减毒活疫苗的保护效果会逐年下降,实施2剂次水痘疫苗免疫策略十分必要。     

儿童接种风疹减毒活疫苗免疫效果调查与分析

目的:评价国产风疹减毒活疫苗初种1年后的免疫效果。方法:利用前瞻性的研究方法,以1~14岁健康儿童的血清中风疹特异性抗体(RV—IgG)阴性者作为观察对象。根据是否接种风疹疫苗分为接种组和对照组,用ELISA方法检测接种前后血清中Rv-IgG的水平。结果:风疹疫苗接种组RV—IgG阳转率为54·13%,对照组自然感染率为39·45%,两组差异有极显著的统计学意义(χ2=25·42,P<0·01)。结论:本地区儿童风疹疫苗的免疫效果有待于进一步提高。     

儿童接种麻疹风疹联合减毒活疫苗的免疫效果观察

目的了解儿童接种麻疹风疹联合减毒活疫苗(简称麻风疫苗)的免疫效果。方法采用分层系统抽样方法抽取宁波市2009年7月1日—9月30日出生的本地儿童,在接种麻风疫苗接种后3个月采集血标本,采用酶联免疫吸附试验检测麻疹IgG和风疹IgG抗体。结果 1053名儿童采血检测,其中男童591人,女童462人;城市520人,农村533人。儿童麻疹、风疹IgG抗体阳性率分别为97.34%和95.25%。麻疹、风疹IgG抗体浓度最小值均为0 mIU/ml,最大值分别为682801.01和23475.72 mIU/ml,平均浓度分别为4233.32和161.74 mIU/ml;农村麻疹IgG抗体平均浓度为5611.55 mIU/ml,高于城市的3171.17 mIU/ml,性别间差异均无统计学意义(P0.05)。结论儿童接种麻风疫苗后,能获得较理想的免疫应答。     

甲型肝炎减毒活疫苗保护效果与应用策略研究

本研究课题旨在应用流行病学、免疫学及应用数学的原理及技术 ,考核我国自行研制的、国际上所独有的甲型肝炎(甲肝 )减毒活疫苗的免疫原性及保护效果 ,并研究符合我国国情的甲肝免疫预防策略。通过课题协作组近 10年的努力 ,我们确定了疫苗的规范化滴度 ;规范化甲肝减毒活疫苗的免疫原性 ,预防发病、感染与暴露后预防效果 ;对比了活疫苗与国外灭活疫苗的免疫原性以及单剂免疫与加强免疫的免疫原性 ;测定了活疫苗免疫后抗体持久性 ;改进了活疫苗滴度的测定方法 ;确定了甲肝疫苗的初免年龄 ,成人免疫效果 ,与免疫球蛋白联合免疫效果 ;测算了不…     

麻疹减毒活疫苗效力的Meta分析

目的了解麻疹减毒活疫苗(MV)效力。方法对国内1998年3月~2007年3月公开发表的符合入选标准的有关MV效力的研究文献,根据各研究结果的一致性,利用随机效应模型或固定效应模型进行Meta分析。结果有7篇文献符合入选标准,均为MV效力的病例对照研究。结果发现MV效力为82.9%[95%可信区间(CI)66.5%~91.7%],低年龄儿童MV效力为85.2%(95%CI:65.2%~93.7%),高年龄儿童MV效力为65.7%(95%CI:42.3%~79.6%)。结论MV效力低于理论的95%,提示为预防和控制麻疹爆发、流行,应提高和维持高水平的MV初免和复种接种率。     

麻疹减毒活疫苗初次免疫月龄对免疫效果影响的Meta分析

目的研究婴儿初次接种麻疹减毒活疫苗(MV)的免疫成功率、抗体几何平均滴度(GMT)与婴儿月龄的关系。方法全面收集同时进行MV 6月龄、8月龄初次免疫并报告了相应免疫成功率、抗体GMT的文献,运用RevMan软件对免疫成功率、抗体GMT进行Meta分析;并对免疫成功率进行敏感性分析。结果共有10篇文献符合纳入标准,8月龄与6月龄初免成功率差值d-=0.06,其95%可信区间(0.03~0.10),8月龄、6月龄抗体GMT的平均数分别为1∶1 539.17、1∶909.60,GMT的比值为1.77(1.13~2.75);免疫成功率的敏感性分析,Z=2.78,P=0.005,不改变原分析结果的性质。结论8月龄接种MV免疫成功率及抗体GMT均可超过6月龄接种,宜采取继续以8月龄为MV初次免疫月龄及开展强化免疫、做好常规免疫的策略来消除麻疹。     

甲型肝炎减毒活疫苗加强免疫效果的初步研究

目的　观察甲型肝炎 (甲肝 )减毒活疫菌 (10 7.0 TCID50 )加强免疫效果 ,并同活疫苗一针法结果进行比较。方法　在河北省正定县选择 42名经事先检测甲肝抗体阴性的易感儿童 ,分别于0、2和 6个月各接种一剂甲肝减毒活疫苗 ,并于接种后 1、2、6、7、9和 12个月采集血清标本 ,观察免后抗体动态变化。结果　第 1剂接种后 1个月抗体阳转率达 81.4% ,第 2剂免后抗体阳转率达 10 0 % ,抗体水平于第 3剂免后 1个月达高峰 ,为 2 739mIU/ml,以后呈下降趋势 ,免后 12个月抗体阳转率仍为 10 0 % ,抗体水平下降至 979mIU/ml。结论　甲型肝炎减毒活疫苗加强免疫能诱导良好的免疫回忆反应 ,其免疫学效果同史克灭活疫苗相当 ,而明显高于活疫苗一针法。活疫苗加强免疫中 ,初免是基础。活疫苗加强免疫会提高疫苗保护效果 ,并延长疫苗的免疫持久性     

Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States

PurposeThis analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013–2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013–2014.MethodsPost hoc analyses of a 2013–2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009–2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location.ResultsFrom the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P < 0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors’ central locations. The review of LAIV VE studies showed that in the 2010–2011 and 2013–2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010–2014.ConclusionsThis study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility of the A/California/7/2009 (H1N1pdm09) LAIV strain to thermal degradation.Clinical trial registry: NCT01997450     

Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity

A recent study of inactivated influenza vaccine (IIV) in children aged 3–8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24–71 months was conducted. Moderate/severe influenza was defined as fever >39 °C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community.     

Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials

Nine randomized clinical trials, including approximately 25,000 children aged 6–71 months and 2000 children aged 6–17 years, have evaluated the efficacy of live attenuated influenza vaccine (LAIV) against culture-confirmed influenza as compared to placebo or trivalent inactivated vaccine (TIV). We conducted meta-analyses, based on Mantel–Haenszel relative risks from fixed effect models, to provide an estimate of vaccine efficacy (VE). Relative to placebo, year 1 VE for two doses in vaccine-naïve young children was 77% (95% CI: 72%, 80%; P < 0.001) against antigenically similar strains and 72% against strains regardless of antigenic similarity. Efficacy was 85%, 76%, and 73% against antigenically similar A/H1N1, A/H3N2, and B, respectively. Year 1 VE of one dose against antigenically similar strains in vaccine-naive children was 60%; efficacy of one dose in previously vaccinated children in year 2 of the various studies was 87%. In head-to-head trials comparing two doses of TIV and LAIV, vaccine-naïve children who received two doses of LAIV experienced 46% fewer cases of influenza illness caused by antigenically similar strains. Similarly, for studies including older children who had been previously vaccinated, those receiving one LAIV dose experienced 35% fewer cases of influenza illness than those receiving one TIV dose. LAIV showed high VE versus placebo with no evidence of difference by age or by circulating subtype. In these studies, LAIV was more effective than TIV.     

Revisiting live attenuated influenza vaccine efficacy among children in developing countries

Seasonal influenza epidemics cause significant pediatric mortality and morbidity worldwide. Live attenuated influenza vaccines (LAIVs) can be administered intranasally, induce a broad and robust immune response, demonstrate higher yields during manufacturing as compared to inactivated influenza vaccines (IIVs), and thereby represent an attractive possibility for young children in developing countries. We summarize recent pediatric studies evaluating LAIV efficacy in developing countries where a large proportion of the influenza-virus-associated respiratory disease burden occurs. Recently, two randomized controlled trials (RCTs) assessing Russian-backbone trivalent LAIV in children reported contradictory results; vaccine efficacy varied between Bangladesh (41 %) and Senegal (0.0 %) against all influenza viral strains. Prior to 2013, Ann Arbor-based LAIV demonstrated superior efficacy as compared to IIV. However, due to low effectiveness of the Ann Arbor-based LAIV against influenza A(H1N1)pdm09-like viruses, the CDC Advisory Committee on Immunization Practices (ACIP) recommended against the use of LAIV during the 2016–17 and 2017–18 influenza seasons. Reduced replicative fitness of the A(H1N1)pdm09 LAIV strains is thought to have led to the low effectiveness of the Ann-Arbor-based LAIV. Once the A(H1N1)pdm09 component was updated, the ACIP reintroduced the Ann-Arbor-based LAIV as a vaccine choice for the 2018–19 influenza season. In 2021, results from a 2-year RCT evaluating the Russian-backbone trivalent LAIV in rural north India reported that LAIV demonstrated significantly lower efficacy compared to IIV, but in Year 2, the vaccine efficacy for LAIV and IIV was comparable. A profounder understanding of the mechanisms underlying varied efficacy of LAIV in developing countries is warranted. Assessing replicative fitness, in addition to antigenicity, when selecting annual A(H1N1)pdm09 components in the Russian-backbone trivalent LAIVs is essential and may ultimately, enable widespread utility in resource-poor settings.     

Efficacy of live attenuated influenza vaccine in children against influenza B viruses by lineage and antigenic similarity

Seasonal influenza vaccines, including live attenuated influenza vaccine (LAIV), contain three vaccine strains (two type A and one type B). Ideally, the hemagglutinin antigens of the recommended vaccine strains are antigenically similar to epidemic wild-type strains; in actuality, the antigenic match between circulating and vaccine strains each year can vary significantly owing to intermittent genetic reassortment and continuous antigenic drift. For influenza B, antigenic relatedness is further complicated by the existence of two distinct lineages. Consequently, the influenza B vaccine component can be of a completely different antigenic lineage from the circulating epidemic strains. Using data from nine randomized clinical trials in young children (6 months to 6 years of age), vaccine efficacy of LAIV against influenza B strains was assessed across this spectrum of antigenic relatedness. In an integrated analysis, vaccine efficacy of two doses of LAIV in vaccine-naive children was 86% against B strains of the same lineage and closely matched to the vaccine strain, 55% against strains of the same lineage but antigenically drifted from the vaccine strain, and 31% against strains of the opposite B lineage and antigenically unrelated to the vaccine strain. These data provide a more accurate assessment of the protection provided by the current trivalent vaccine and highlight the need for vaccination strategies that provide enhanced protection against both lineages of influenza B such as a quadrivalent influenza vaccine.     

The role of nasal IgA in children vaccinated with live attenuated influenza vaccine

Background

Immunoglobulin A (IgA) is the predominant antibody produced in response to mucosal infections. The role of IgA in providing protection against influenza in children vaccinated with live attenuated influenza vaccine (LAIV) has not been well described.

Methods

Nasal IgA responses were assessed using data from 3 prospective, 2-year, randomized studies comparing LAIV with placebo in children 6–36 months of age. In each study, samples were collected in a subset of patients; a new cohort was enrolled each year. Ratios of strain-specific nasal IgA to total nasal IgA were calculated and prevaccination to postvaccination geometric mean fold-rises (GMFRs) were evaluated. Mean postvaccination IgA ratios were compared for subjects with and without confirmed influenza illness by study and in pooled analyses.

Results

Across studies, a higher percentage of children receiving LAIV had a ≥2-fold increase in strain-specific IgA ratio compared with placebo recipients. GMFRs after LAIV in years 1 and 2 ranged from 1.2 to 6.2, compared with 0.5–2.2 among placebo recipients. Similar responses were observed in subjects who were baseline seronegative and seropositive based on serum hemagglutination inhibition antibody titers. In years 1 and 2, the mean postvaccination strain-specific to total IgA ratio was 3.1-fold (P < 0.01) and 2.0-fold (P < 0.03) higher among LAIV recipients with no evidence of culture-confirmed influenza illness compared with LAIV recipients who developed culture-confirmed influenza illness; a similar and consistent trend was observed for each individual study and type/subtype.

Conclusions

The current analysis demonstrates that nasal IgA contributes to the efficacy of LAIV and can provide evidence of vaccine-induced immunity. However, the inherent heterogeneity in nasal antibody levels and variability in nasal specimen collection hinders the precise evaluation of mucosal antibody responses. Other studies have demonstrated that LAIV-induced immunity is also partially explained by T-cell immunity, serum antibody responses, and innate immunity, consistent with the multi-faceted nature of immunity induced by wild-type influenza infection and other live virus vaccines.     

The safety and effectiveness of self-administration of intranasal live attenuated influenza vaccine in adults

Intranasal live attenuated influenza vaccine (LAIV) has potential for self-administration (SA) by adults and adolescents, which could save time and cost in mass vaccination settings. Participants in a study of LAIV in adults (n = 4561) selected either SA or health care provider (HCP) administration and were followed for febrile illness during the influenza season. More LAIV recipients chose SA-LAIV (72%) than HCP-LAIV (28%). Overall, 97% of SA-LAIV and 98% of HCP-LAIV recipients had no problems with vaccine administration. Four of 13 study sites enrolled more than 50 subjects in both cohorts. Overall and for these 4 sites, illness incidence was similar with SA-LAIV and HCP-LAIV. Solicited reactogenicity events and adverse events through 7 days post vaccination were comparable for SA-LAIV and HCP-LAIV recipients; both groups exhibited increased runny nose, sore throat, and cough relative to placebo recipients. SA-LAIV and HCP-LAIV appeared similarly effective against influenza-like illness and had comparable safety profiles.     

Influence of maternally-derived antibodies on live attenuated influenza vaccine efficacy in pigs

Vaccination during pregnancy is practiced in swine farms as one measure to control swine influenza virus (SIV) infection in piglets at an early age. Vaccine-induced maternal antibodies transfer to piglets through colostrum and stabilize the herd: however, maternally derived antibodies (MDA) interfere with immune response following influenza vaccination in piglets at the later stage of life. In addition, MDA is related to enhanced respiratory disease in SIV infection. Previously, we have developed a bivalent live attenuated influenza vaccine (LAIV) which harbors both H1 and H3 HAs. We demonstrated vaccination of this LAIV provided protection to homologous and heterologous SIV infection in pigs. In this study we aimed to investigate the influence of MDA on LAIV efficacy. To this end, SIV sero-negative sows were vaccinated with a commercial vaccine. After parturition, nursery piglets were vaccinated with LAIV intranasally or intramuscularly, and were then challenged with SIV. We report that MDA hampered serum antibody response induced by intramuscular vaccination but not by intranasal vaccination of the LAIV. Viral challenge in the presence of MDA caused exacerbated respiratory disease in unvaccinated piglets. In contrast, all LAIV vaccinated piglets were protected from homologous viral infection regardless of the route of vaccination and the presence of MDA. Our results demonstrated that LAIV conferred protection in the presence of MDA without inciting exacerbated respiratory disease.     

A multinational,randomized, placebo-controlled trial to assess the immunogenicity,safety, and tolerability of live attenuated influenza vaccine coadministered with oral poliovirus vaccine in healthy young children

Live attenuated influenza vaccine (LAIV) provides a useful tool to rapidly immunize populations in the developing world to prevent influenza outbreaks. In this noninferiority trial conducted in Asia and South America, where oral poliovirus vaccine (OPV) is still used, 2503 children aged 6 to <36 months with three polio immunizations were randomized to receive LAIV + OPV, placebo + OPV, or LAIV only. Immune responses in children receiving concomitant LAIV + OPV were noninferior to those observed in recipients of either vaccine alone. Response rates for different poliovirus types were similar in recipients of LAIV + OPV and placebo + OPV. Response rates to all influenza strains were similar in LAIV + OPV and LAIV-only recipients. Concomitant OPV and LAIV were safely administered to young children.     

Genetic stability of live attenuated vaccines against potentially pandemic influenza viruses

BackgroundEnsuring genetic stability is a prerequisite for live attenuated influenza vaccine (LAIV). This study describes the results of virus shedding and clinical isolates’ testing of Phase I clinical trials of Russian LAIVs against potentially pandemic influenza viruses in healthy adults.MethodsThree live attenuated vaccines against potentially pandemic influenza viruses, H2N2 LAIV, H5N2 LAIV and H7N3 LAIV, generated by classical reassortment in eggs, were studied. For each vaccine tested, subjects were randomly distributed into two groups to receive two doses of either LAIV or placebo at a 3:1 vaccine/placebo ratio. Nasal swabs were examined for vaccine virus shedding by culturing in eggs and by PCR. Vaccine isolates were tested for temperature sensitivity and cold-adaptation (ts/ca phenotypes) and for nucleotide sequence.ResultsThe majority of nasal wash positive specimens were detected on the first day following vaccination. PCR method demonstrated higher sensitivity than routine virus isolation in eggs. None of the placebo recipients had detectable vaccine virus replication.All viruses isolated from the immunized subjects retained the ts/ca phenotypic characteristics of the master donor virus (MDV) and were shown to preserve all attenuating mutations described for the MDV. These data suggest high level of vaccine virus genetic stability after replication in humans.During manufacture process, no additional mutations occurred in the genome of H2N2 LAIV. In contrast, one amino acid change in the HA of H7N3 LAIV and two additional mutations in the HA of H5N2 LAIV manufactured vaccine lot were detected, however, they did not affect their ts/ca phenotypes.ConclusionsOur clinical trials revealed phenotypic and genetic stability of the LAIV viruses recovered from the immunized volunteers. In addition, no vaccine virus was detected in the placebo groups indicating the lack of person-to-person transmission.LAIV TRIAL REGISTRATION at ClinicalTrials.gov: H7N3-NCT01511419; H5N2-NCT01719783; H2N2-NCT01982331.