流感疫苗接种人群抗体水平监测分析

目的 了解人群甲型H1N1流感(pH1N1)疫苗接种后抗体水平变化规律、持续时间以及疫苗接种的免疫效应.方法 应用微量血凝抑制试验(HI)方法对人群免疫前及免疫后1、2、3、7、14个月进行血清抗体检测.结果 免疫前各组人群的pH1N1流感抗体水平较低,1个月后抗体滴度明显上升,并随着时间的延长逐渐下降.VTH组接种季节性流感疫苗后pH1N1抗体滴度上升不明显,而再接种pH1N1流感疫苗后pH1N1抗体滴度升至1∶93,显著低于同期VH组的抗体水平(1∶245).VHT组接种pH1N1疫苗后pH1N1抗体滴度为1∶272,而再进行接种季节性流感疫苗后pH1N1抗体滴度降至1∶196,低于VH组(1∶259),差异无统计学意义(P＞0.05).结论 pH1N1流感疫苗免疫人群的抗体水平随着时间的延长逐渐下降,抗体减弱或消失时提示应重新进行疫苗接种；提前接种季节性流感疫苗可使pH1N1流感抗体水平下降.     

甲型H1N1流感疫苗免疫效果及影响因素研究

目的了解学生大规模接种甲型H1N1流感疫苗的免疫效果及影响因素,为探索甲型H1N1流感免疫策略和防控措施提供科学依据。方法分别对344名中学生在甲型H1N1流感疫苗接种前及接种后1个月采集血清标本,进行抗体水平的检测。并收集中学生在接种疫苗前季节性流感疫苗接种史、流感样症状等有关流行病学信息,评价甲型H1N1流感疫苗的免疫效果及影响因素。结果 344名中学生在免前H1N1流感抗体几何平均滴度(GMT)为1∶16.97(95%CI:1∶14.49~1∶19.86),抗体阳性率为36.50%(95%CI:31.35%~41.89%);免后GMT为1∶167.41(95%CI:1∶145.08~1∶193.18),阳性率为89.91%(95%CI:86.19%~92.91%),阳转率为72.54%(95%CI:67.76%~77.32%),均明显高于免前。接种疫苗前3个月的季节性流感疫苗接种史、流感样症状史等因素分组后,各组间免疫学效果指标间差异无统计学意义(P>0.05)。结论接种甲型H1N1流感疫苗后免疫成功率70%以上,符合欧盟和美国FDA的有关规定,免疫效果良好。季节性流感疫苗接种史、流感症状史等对疫苗的免疫学保护效果无明显影响。     

2009年华容县健康人群甲型H1N1流感疫苗免疫效果分析

目的了解健康人群接种甲型H1N1流感疫苗后的免疫效果及抗体水平。方法观察接种甲型H1N1流感疫苗人群中不良反应的发生情况;按照不同的年龄组随机抽取350人,采用描叙性流行病学方法,对疫苗的安全性和有效性进行评价;微量血凝抑制试验检测接种者甲型H1N1流感病毒抗体,SPSS16.0统计学软件对接种30 d后甲型H1N1流感与普通流感的发病率、就诊率及HI抗体阳转率进行比较。结果接种组接种甲型H1N1流感疫苗30 d后甲型H1N1流感与普通流感的发病率与就诊率均低于对照组,差异有统计学意义（P〈0.05）;接种甲型H1N1流感疫苗人群中共出现不良反应1 891例,总不良反应率为4.35%;接种组总体HI抗体阳转率显著高于对照组（χ2=4.27,P〈0.05）,达到欧盟药品评价委员会的标准,各年龄组间HI抗体阳转率差异无统计学意义。结论国产甲型H1N1流感疫苗具有较高的安全性与较好的免疫原性,适合在健康人群中普遍接种。     

北京市顺义区健康人群甲型H1N1流感抗体水平及其疫苗免疫效果

目的了解北京市顺义区健康人群甲型H1N1流感抗体水平,评价甲型H1N1流感疫苗免疫效果,为卫生部门制定预防控制措施和策略提供依据。方法随机选取顺义区12个乡街的5岁以上健康人群(202名)采集免疫前静脉血检测抗体,评估健康人群抗体水平;接种甲型H1N1流感疫苗后,各年龄组随机选取部分人群做免疫后抗体水平检测,评估疫苗免疫效果。结果 202份血清标本中甲型H1N1流感抗体水平阳性率46.53%(94/202),与北京市人群甲型H1N1流感抗体水平检测结果差异有统计学意义。抗体几何平均滴度倒数(GMRT)为32.78。不同性别人群之间甲型H1N1流感抗体阳性率差异无统计学意义,不同年龄组之间抗体水平阳性率差异有统计学意义,25~29岁、10~14岁组抗体水平阳性率高。50名评估对象免疫前抗体阳性率50%(25/50),免疫后抗体阳性率94%(47/50),甲型H1N1流感抗体阳转率80%(30/50)。免疫前阴性和阳性评估对象之间抗体阳转率差异有统计学意义。评估对象总体抗体滴度呈6倍增高,各年龄组免疫前、后抗体GMRT的变化之间差异有统计学意义,25~29岁、60岁以上组滴度升高倍数最低。结论顺义区甲型H1N1流感实际感染数高于北京市甲型H1N1流感平均感染水平。疫苗接种使目标人群达到了形成该样本人群免疫屏障的要求,提示在甲型H1N1流感大流行之际接种疫苗是控制疫情的必要手段。免疫前抗体水平、年龄是甲型H1N1流感抗体阳转率的影响因素。     

江苏省甲型H1N1流感裂解疫苗的免疫效果分析

2009年甲型H1N1流感的流行引起了广泛重视,接种疫苗是预防流感流行、降低死亡率和病死率的最有效方法[1],本研究通过比较不同人群甲型H1N1抗体水平变化趋势,初步评估甲型H1N1流感裂解疫苗的免疫效果. 1.对象与方法: (1)研究对象:2009年11月、12月、2010年2月,在江苏省随机选择甲型H1N1流感疫苗接种人群(免疫人群),连续采集同一批人群(共281人)免疫前、免疫后1个月及3个月的血清标本(排除季节性流感疫苗接种者和接种前1个月内有流感样症状者);连续采集甲型H1N1流感确诊病例(发病时间为2009年10月15日至11月15日,经RT-PCR检测确诊为甲型H1N1流感病毒感染[1])同一组病例发病2周内(107例)、发病后1个月(77例)及3个月(52例)的血清标本(排除甲型H1N1流感疫苗和季节性流感疫苗接种者),选择同时期自然人群作为背景资料.     

初中生甲型H1N1流感疫苗接种效果分析及抗体水平监测

目的了解初中生接种甲型H1N1流感疫苗的流行病学效果及抗体水平。方法采用非随机对照临床试验方法,选择9 123名初中生,分甲型H1N1流感疫苗接种组(3 726人)和对照组(5 397人),随访观察一个流行周期(6个月),比较两组流感样病例、甲型H1N1流感病例、季节性流感病例的发生率及接种前后阳性率和阳转率。结果接种组与对照组除甲型H1N1流感发病密度(接种组:0/1 000人年,对照组:2.22/1 000人年)差异有统计学意义外(P=0.0121),其他流感相关疾病(流感样病例、乙型流感、流感病毒核酸阳性)发病密度差异无统计学意义(P>0.05);不管是接种组还是对照组,不同住宿情况(住校和走读)流感样病例发生差异均有统计学意义,接种组中,季节性流感接种对乙型流感和流感病毒核酸阳性差异均有统计学意义;对照组中,流感症状史对甲型H1N1、乙型流感和流感病毒核酸阳性差异均有统计学意义;疫苗接种前与接种后1个月比较,流感抗体几何平均滴度(GMT)与阳性率都增高(P<0.05)。结论初中生大规模接种甲型H1N1流感疫苗能有效预防甲型H1N1流感,其免疫及保护效果良好,住校生较走读生更易发生流感样病例,疫苗接种可能不存在交叉保护作用。     

重庆市3所医疗机构2014人甲型H1N1流感血清流行病学分析

[目的]了解对医疗机构就诊者甲型H1N1流感抗体水平现状,为制定针对性的防治措施提供依据.[方法]对1 367名门诊病例、277名健康体检人群和370名献血者进行流行病学调查并采集血清进行甲型H1N1流感血凝抑制(HI)试验.[结果]HI试验总体阳性率为11.8％ (95％CI:10.5％～13.3％),高滴度者(≥1:320)占阳性数的11.3％（95％CI:7.0％～15.6％),2周前出现过流感样症状之间、5～年龄组与其余3个年龄组间和是否接种甲型H1N1流感疫苗之间阳性几何平均倒数滴度(GMRT)的差异有统计学意义(P＜ 0.05);Logistic回归分析结果均显示抗体阳性率与年龄、接种甲型H1N1流感疫苗和2周前出现过流感样症状者有统计学意义.[结论]重庆市甲型H1N1流感免疫水 平较低,易发生流行,及时接种甲型H1N1流感疫苗可提高人群免疫水平.     

深圳市宝安区托幼机构人员甲型H1N1流感疫苗接种率及其影响因素

目的 了解深圳市宝安区托幼机构人员甲型H1N1流行性感冒(甲流)疫苗接种率及其影响因素.方法 随机抽取深圳市宝安区100家托幼机构530人作为面访匿名问卷调查对象.采用描述性分析、秩和检验、x 2检验和Logistic回归分析分别对疫苗接种率的影响因素进行单因素和多因素分析.结果 深圳市宝安区托幼机构人员甲型H1N1流感疫苗接种率为39.96％,未接种的主要原因是怕出现疫苗不良副反应,占39.10％.性别为男性[男性:比值比(Odds Ratio,OR)=3.193,95％可信区间(Confidence Interval,CI)=1.285～7.936];工作岗位为保健医生和保育人员(保健医:OR=12.583,95％ CI=2.825 ～56.082;保育员:OR =7.581,95％ CI=1.881～30.554)、工作年限为11～ 15年(11 ～ 15年:OR=6.299,95％CI=1.169～33.945)和近3年接种过季节性流感疫苗(接种过:OR=8.856,95％CI=4.139～ 18.703;不清楚:OR =4.322,95％CI=1.588～ 11.766)对疫苗接种率有影响.结论 深圳市宝安区托幼人员甲流疫苗接种率较高,应加强甲流疫苗有效性和安全性的宣传,特别要针对女性、教师、工作年限小于11年、大于15年和近3年无季节性流感疫苗接种史等人群.     

无锡市甲型H1N1流感及季节性流感疫苗接种效果分析

目的调查流感样病例(ILI)和无锡市一般人群中甲型H1N1流感疫苗及季节性流感疫苗的接种情况,评估疫苗接种后对人群的保护效果。方法以无锡市2家哨点医院为基础,采集流感样病例病毒核酸检测阳性的病例作为病例组,共1 529人,同时按照"病例"的电话信息,随机产生电话号码选择、年龄匹配的一般人群作为对照组,共380人。结果病例组甲型H1N1流感疫苗接种率为6.1%(94/1 529),对照组甲型H1N1流感疫苗接种率为12.1%(46/380),两组比较,差异有统计学意义(P0.01);甲型H1N1流感病例中接种甲型H1N1流感疫苗的比例为12.5%(3/24),门诊检测阴性的ILI病例接种甲型H1N1流感疫苗的比例为6.1%(78/1 273),"接种甲型H1N1流感疫苗"因素的OR值为0.457(P=0.201);以电话调查一般人群(330例)作为对照组,接种甲型H1N1流感疫苗的比例为13.3%(44/330),OR值为1.077(P=0.908)。结论该次调查说明接种甲型H1N1流感疫苗对预防流感样病例有一定效果,但由于样本量较少,24种方法病例对照分析均未得出差异有统计学意义。     

甲型H1N1流感疫苗接种对其暴发疫情的影响

目的了解甲型H1N1流感(甲流)疫苗接种后对甲流暴发疫情的影响。方法对2011年4—5月发生在学校的1起甲流暴发疫情进行流行病学描述性分析,用回顾性队列研究的方法分析甲流疫苗接种对该起暴发疫情的影响。结果该校542名师生中191人患病,罹患率为35.24%,发病时间主要集中在4月19—25日,发病人群主要为1～6年级的小学生(χ2=9.972,P0.01),住校生发病高于非住校生,112名接种过甲流疫苗的师生发病率为16.96%,明显低于未接种疫苗的师生(40%),差异有统计学意义(χ2=20.661,P0.05),OR=0.306(95%CI∶0.180～0.521)。结论接种甲流疫苗可以有效预防甲型H1N1流感的发生,减少暴发疫情的发病率。     

Pandemic influenza A/H1N1 vaccine administered sequentially or simultaneously with seasonal influenza vaccine to HIV-infected children and adolescents

In order to evaluate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to HIV-infected children and adolescents, 36 HIV-infected children and adolescents, and 36 age- and gender-matched healthy controls were randomised 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine one month later, or to receive the pandemic and seasonal vaccines simultaneously upon enrolment. Seroconversion and seroprotection rates against the pandemic influenza A/H1N1 virus were 100% two months after vaccine administration in both groups, regardless of the sequence of administration. Geometric mean titres against pandemic and seasonal antigens were significantly higher when the seasonal and pandemic vaccines were administered simultaneously than when the seasonal vaccine was administered alone. Local and systemic reactions were mild and not increased by simultaneous administration. In conclusion, the 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine is as immunogenic, safe and well tolerated in HIV-infected children and adolescents as in healthy controls. Its simultaneous administration with virosomal-adjuvanted seasonal antigens seems to increase immune response to both pandemic and seasonal viruses with the same safety profile as that of the pandemic vaccine alone. However, because this finding cannot be clearly explained by an immunological viewpoint, further studies are needed to clarify the reasons of its occurrence.     

Unadjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected adults

We evaluated the immune response to a 2009 influenza A (H1N1) unadjuvanted vaccine in HIV-infected patients and assessed the boosting effect of a second dose. HIV-infected adults were enrolled and scheduled to receive the H1N1 unadjuvanted vaccine containing 15 μg of A/California/7/2009 haemagglutinin. Anti-H1N1 antibody titers were measured at enrollment and 4-8 weeks after each vaccination by using haemagglutination inhibition (HI) and virus neutralization (NT) assays. One hundred and four patients were analyzed. Seroconversion, as measured by using HI and NT assays, was observed in 52 (50.0%) patients and 49 (47.1%) patients, respectively, after the first dose. Seroconversion rate evaluated by using NT, but not HI, antibody titers was associated with HIV RNA levels of <400 copies/ml (odds ratio, 3.21; 95% CI, 1.15-8.96). Other parameters, including CD4 cell count, were not associated with seroconversion. In a cohort that received two vaccine doses at a 4-8-week interval (n = 54), the seroconversion rate and geometric mean titer for HI antibodies were 44.4% (95% CI, 30.8-58.1%) and 30.5 (95% CI, 19.9-46.9) after the first dose, respectively, and 48.1% (95% CI, 34.4-61.9%) and 39.0 (95% CI, 26.1-58.2) after the second dose, respectively. Among HIV-infected patients, the seroconversion rate was around 50% after the first dose of unadjuvanted vaccine. A second dose of vaccine had a limited boosting effect on immunity in this patient cohort.     

Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

Background

Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.

Methods

An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18–59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed.

Results

A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008–09 or 2009–10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000–01 to 2006–07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever.

Conclusions

A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.     

Protection of trivalent inactivated influenza vaccine against hospitalizations among pandemic influenza A (H1N1) cases in Argentina

The aim of this study was to estimate the effectiveness of 2009 seasonal trivalent inactivated vaccine in reducing hospitalizations due to the novel influenza A H1N1 virus among positive cases. Data collected from Argentina's national epidemiological surveillance system were analyzed. All patients had a clinical diagnosis and underwent positive serological tests for pandemic influenza A H1N1. Logistic regression was used to estimate vaccine effectiveness to prevent severe cases of the disease, measured as hospitalizations. The adjusted effectiveness of the vaccine was 50% (95% CI: 40–59%). Vaccination was significantly associated with hospitalizations in all age groups, and within groups that had and had not received antiviral treatment. These results suggest that seasonal influenza vaccine might have conferred partial protection against severe cases due to the novel pandemic influenza.     

Immunogenicity of inactivated 2009 H1N1 influenza vaccine in pediatric liver transplant recipients

To assess the safety and immunogenicity of 2009 H1N1 influenza vaccination, 13 pediatric liver transplant recipients and 31 immunocompetent controls received inactivated influenza vaccine without adjuvant according to Japanese guidelines. Serious adverse events and acute allograft rejections were not observed in participants. Seroprotection rates (hemagglutinin-inhibition (HI) antibody titer ≥ 1:40) were 53.8% among recipients and 58.1% among controls (p = 0.797). Seroconversion rates (4-fold or more HI antibody rise) were 46.2% for the recipient group and 51.6% for the control group (p = 0.741). Geometric mean titers were elevated after vaccination in both groups. In comparison with the seasonal influenza vaccination, the seroconversion rate for 2009 H1N1 appeared to be higher than that for seasonal influenza antigens, and the seroprotection rate for 2009 H1N1 clearly increased after vaccination. These findings suggest that pediatric liver transplant patients may respond safely to inactivated 2009 H1N1 influenza vaccines in a manner similar to immunocompetent children.     

Safety and immunogenicity of a replication-deficient H5N1 influenza virus vaccine lacking NS1

BackgroundTraditional inactivated influenza vaccines are the type of vaccines that were most frequently developed for immunization against the highly pathogenic avian H5N1 influenza virus. However, clinical trials with inactivated influenza vaccines for H5N1 indicated that high doses and at least two immunizations are required for an effective immune response (Nicholson et al., 2001; Treanor, Campbell et al., 2006; Treanor, Schiff et al., 2006; Ehrlich et al., 2008). We investigated the safety and immunogenicity of a live attenuated H5N1 vaccine (delNS1-H5N1) lacking the interferon antagonist nonstructural protein 1 (NS1).MethodsWe conducted a double-blind, placebo-controlled, phase 1 study in healthy adult participants who were randomly assigned at a 2:1 ratio to receive two immunizations of delNS1-H5N1 vaccine at 6.8 log10 50% tissue culture infectious doses (TCID₅₀)/subject or 7.5 log10 TCID₅₀/subject, or placebo.ResultsIntranasal vaccination with the live attenuated delNS1-H5N1 vaccine was safe and well tolerated. The most common adverse events identified were symptoms associated with mild influenza infections, such as increased body temperature (>37.0 °C), pharyngeal erythema, rhinitis and throat irritation, and were reported within 7 days after the first immunization. delNS1-H5N1 was able to induce significant vaccine-specific serum antibody titers even at the lower dose level of 6.8 log10 TCID₅₀/subject. Seroconversion occurred in 75% of study participants after only one immunization with 7.5 log10 TCID₅₀/subject. Vaccine-specific local IgA responses were observed in 41.7% of individuals that showed serum antibody responses after 2nd immunization.ConclusionsWe show that vaccination with a live attenuated H5N1 influenza vaccine lacking NS1 is safe and induces significant levels of vaccine-specific antibodies even after one immunization. The safety and immunogenicity data indicate that delNS1-H5N1 has the potential to fulfil the unmet need for an effective influenza vaccine in pandemic situations. (ClinicalTrials.gov identifier NCT03745274).     

Safety and immune responses following administration of H1N1 live attenuated influenza vaccine in Thais

Background

Emergence and rapid spread of influenza H1N1 virus prompted health authorities to develop a safe and effective influenza vaccine for domestic use. The Thai Government Pharmaceutical Organization (GPO) with technical support from Russia through WHO had prepared a pandemic live attenuated vaccine (PLAIV) using ca-ts attenuated candidate strain A/17/CA/2009/38 (H1N1) for Thais.

Methods

Each participant received two doses of intranasal H1N1 vaccine or placebo 21 days apart. All were followed up at 7, 21, 42 and 60 days after first immunization. Blood was drawn for hemagglutination inhibition (HAI) assay from all participants at days 1, 21, 42, and 60 after first immunization. A subset of 40 participants aged 19–49 years was randomly selected for nasal washing at days 1, 21, 42, and 60 to assess IgA using direct enzyme-linked immunosorbent assay (ELISA) along with serum HAI and microneutralization (MN) assay determination.

Results

A total of 363 subjects aged 12–75 years were randomized into 2 groups (271 vaccinees:92 placebos). Almost all AEs were mild to moderate. Local reactions were stuffy nose (22.3%), runny nose (25.1%), scratchy throat (27.2%) and sore throat (19.3%). Systemic reactions included headache (21.7%), myalgia (13.8%), fatigue (16.8%) and postnasal drip (19.9%). On day 60, HAI seroconversion rates for vaccine:placebo group were 30.3:6.0 for ITT and 29.4:5.1 for PP analysis. Children showed highest seroconversion rate at 44, but it decreased to 39.4 when all 3 assays (HAI, MN assay and ELISA) from subgroup analysis were considered.

Conclusion

The vaccine candidate is safe. The use of more than one assay may be needed for evaluation of immune response because live attenuated vaccines could effectively induce different kinds of responses. Different individuals could also mount different kinds of immune response, even to the same antigen.