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。     

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.     

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.     

Safety and immunogenicity of inactivated monovalent influenza A/H1N1 vaccine candidate manufactured in Vietnam

We tested a new A/H1N1 inactivated influenza vaccine (IIV) manufactured by Institute of Vaccines and Medical Biologics (IVAC), Vietnam in 48 adults in a Phase 1, double-blinded, randomized, placebo-controlled trial. Two doses of unadjuvanted vaccine or placebo were administered three weeks apart. The vaccine was well tolerated with only transient mild local reactions and low-grade fever in a small proportion of the subjects. One serious adverse event considered unrelated to the study product was reported. The IVAC vaccine proved to be highly immunogenic with 91 percent (95% CI: 0.78, 1) of the subjects developing a ≥4 fold immune responses by hemagglutination inhibition (HAI) assay, and 96 percent (95% CI: 0.78, 1) by the microneutralization (MN) assay. Post-vaccination geometric mean titers (GMTs) were 283.7 (95% CI: 161.7, 497.5) in the HAI and 725.7 (95% CI: 411.3, 1280.3) in the MN assay. These promising results merit further development of the vaccine.ClinicalTrials.gov number: NCT01507779.     

Dose sparing intradermal trivalent influenza (2010/2011) vaccination overcomes reduced immunogenicity of the 2009 H1N1 strain

Background

We hypothesized that low dose intradermal vaccination of the trivalent influenza vaccine (TIV) delivered by the MicronJet600™ (NanoPass Technologies, Israel) would be non-inferior to the full dose intramuscular and mid dose Intanza^® vaccination in the elderly and the chronically ill adults.

Methods

We performed a prospective randomized trial on elderly and chronically ill adults. Subjects were randomly assigned into 4 groups. Groups ID3 and ID9 received reduced dose ID TIV (3 μg and 9 μg of hemagglutinin (HA) per strain respectively) delivered by MicronJet600™ (NanoPass Technologies, Israel). Group INT9 received reduced dose ID TIV (9 μg) delivered by Becton Dickinson's Soluvia™ device (Intanza^®9, Sanofi-Pasteur, France). Control group IM15 received a full dose IM TIV (15 μg). We measured antibody titers by hemagglutination inhibition (HAI) and microneutralization (MN) assays at baseline and day 21.

Results

Baseline characteristics for all groups were similar (group and sample sizes: ID3 = 63; ID9 = 68; INT9 = 65; and IM15 = 66). At day 21 post vaccination, the GMT ratio and the seroconversion rates difference for all three strains of the ID vaccine groups were non-inferior to the IM vaccine group. The seroconversion rate, seroprotection rate, and the GMT of the H1N1 strains by HAI and MN assays were significantly higher in the ID groups compared with the full dose IM vaccine group. The seroconversion rates of the H3N2 strain by HAI assay were also significantly higher in the ID groups when compared with the full dose IM group. Direct comparison among the three ID groups showed no significant differences. No serious adverse events related to vaccination were reported.

Conclusion

Dose-sparing ID TIV can overcome reduced immunogenicity of the H1N1 strain, and according to some measures, for the H3N2 strain. At risk subjects indicated for the TIV should be considered for intradermal immunization to compensate for reduced immunogenicity.     

Pandemic whole-virion,Vero-cell-derived,adjuvant-free influenza A H1N1 vaccine in patients with solid tumors and hematologic malignancies receiving concurrent anticancer treatment: Immunogenicity,tolerability, and acceptability during the pandemic situation

Patients with malignancies are considered to be at increased risk of acquiring influenza. Because of higher complication and case fatality rates, preventive measures such as vaccination are of great interest. The objective of this study was to assess the acceptability, tolerability and immunogenicity of an adjuvant-free whole-virion pandemic influenza A (H1N1) vaccine in cancer patients with ongoing anticancer treatment during a ‘pandemic situation’. Adult patients with hematologic malignancies or solid tumors and concurrent cytotoxic, targeted, and/or hormone therapy were recruited during the influenza A (H1N1) pandemic in 2009/2010 and were offered free vaccine. Antibody titers were measured using virus-specific hemagglutination inhibition assay and ELISA. Among 285 patients with solid tumors who were offered vaccination during their therapy, 260 (91.2%) declined and 25 (8.8%) accepted. Seventeen patients with hematologic malignancies were also vaccinated during therapy; 23 healthy individuals served as a control group. When measured using hemagglutination-inhibition assays, rates of seroprotection, seroconversion, and geometric mean titer ratios after the second vaccination were 96%, 70%, and 4.1 respectively among the healthy individuals, 90%, 52%, and 4.3 among patients with solid tumors, and 67%, 13%, and 1.5 among patients with hematologic malignancies during therapy (P < 0.05). When measured using ELISA, seropositivity differed significantly among the three groups after the second vaccination: healthy individuals 74%, patients with solid tumors 57%, those with hematologic malignancies 13% (P < 0.001). The vaccine was well tolerated. Our results demonstrate a low uptake of the well tolerated adjuvant-free influenza A (H1N1) vaccine by cancer patients receiving anticancer treatment during the pandemic of 2009/2010. Among the vaccinated patients, the immune response was weaker than that in healthy individuals. The immune response in patients with hematological malignancies was low. Two doses of vaccine are needed in these immunosuppressed patients.     

云南保山市甲型H1N1流感病毒裂解疫苗应急接种效果分析

目的 了解保山市2009～2010年甲型H1N1流感病例的分布特征及疫苗控制效果,为甲型H1N1流感防控及疫苗的科学使用提供依据.方法 回顾性分析接种疫苗前后保山市甲型H1N1流感发病人群的分布特征,并比较接种前后甲型H1N1流感发生情况.结果 该市总人口接种率为6.26％,其中学生接种率最高为73.44％.甲型H1...     

Immune response to influenza A (H1N1)v monovalent MF59-adjuvanted vaccine in HIV-infected patients

Immunogenicity of influenza A (H1N1)v MF59-adjuvanted vaccine was studied in HIV-infected patients. The vaccine was effective in inducing a protective immune response in patients with a CD4 >200 cells/μL while individuals with CD4 <200 cells/μL showed lower rates of seroconversion and seroprotection. These results underscore the usefulness of immunization against influenza in HIV-infected patients, though a boosting dose of vaccine may be required in seriously immunocompromised patients.     

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.     

Immunogenicity and tolerability of an inactivated and adjuvanted pandemic H1N1 influenza vaccine, in HIV-1-infected patients

We evaluated the efficacy and tolerability of a single dose of the split virion AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in 84 HIV-1 infected individuals. Antibody titers were determined by hemagglutination inhibition assay and by microneutralization. Vaccine was well tolerated. At 21 days post vaccination, 56 (67%) patients had seroconverted. There was no correlation between baseline CD4 cell count (p = 0.539) or HIV viral load (p = 0.381) and immune response. Other vaccine strategies should be evaluated in this HIV population, to improve response rates.     

2009年上海市甲型H1N1流感疫苗大规模人群接种免疫学效果评价

目的评价2009-2010年上海市甲型H1N1流行性感冒疫苗(甲流疫苗)的免疫学效果。方法以公安人员、中小学生、医务人员这三类重点人群作为免疫学评价的对象,采用分层抽样的方法在上海市4个区县抽取公安人员110人,中小学生146人,医务人员306人,于甲流疫苗接种前和接种后5~6周分别采集外周静脉血,检测甲型H1N1流感(甲流)抗体水平,进行甲流疫苗免疫学效果评价。结果总体上,甲流抗体阳性率由接种前34.9%提高到98.9%,抗体几何平均滴度(GMT)由接种前1∶17提高到1∶351,抗体≥4倍增长率为85.6%。结论 2009年上海市大规模人群接种的甲流疫苗具有良好的免疫学效果。     

Immunogenicity of heterologous H5N1 influenza booster vaccination 6 or 18 months after primary vaccination in adults: A randomized controlled clinical trial

BackgroundHighly pathogenic avian influenza A/H5N1 viruses continue to circulate in birds and infect humans causing serious illness and death.MethodsIn this randomized, observer-blinded study, adults ≥18 years of age (n = 841) received 3.75 or 7.5 μg hemagglutinin antigen (HA) of an AS03-adjuvanted (AS03_A or AS03_B) A/Indonesia/5/2005 H5N1 (subclade 2.1) vaccine (priming), followed by the same HA dose of AS03-adjuvanted A/turkey/Turkey/1/05 H5N1 (clade 2.2) influenza vaccine as a booster 6 or 18 months after priming; an unprimed group received placebo at Day 0, and 3.75 μg HA of AS03_A-adjuvanted booster vaccine at 6 and 18 months. Antibody responses were assessed by hemagglutination-inhibition assay (HI). Microneutralization (MN) antibody and cellular immunoassays were assessed in a subset of participants.ResultsGeometric mean titers (GMTs) and seroconversion rates (SCRs) were higher in primed vs. unprimed subjects against the booster strain 10 days following booster vaccination at month 6 and month 18. After the booster at 18 months, the lower limit of the 97.5% confidence interval for the difference in SCR and GMT ratios between primed and unprimed subjects was >15% and >2.0, respectively, fulfilling the primary endpoint criteria for superiority against the booster strain. MN and cellular immune responses corresponded with the immunogenicity seen in HI measures.ConclusionsAdults primed with a dose-sparing oil-in-water adjuvanted H5N1 subclade vaccine had rapid and durable antibody responses to a heterologous subclade boosting vaccine given 6 or 18 months later.     

Safety and immunogenicity of a 2009 influenza A (H1N1) vaccine in hemodialysis patients

A worldwide vaccination campaign against the 2009 pandemic influenza A (H1N1) virus was launched among high-risk subjects, including hemodialysis patients. The long-term immunogenicity of an influenza vaccine has not been investigated in hemodialysis patients. This study aimed to (1) assess the long-term immunogenicity of a monovalent non-adjuvanted influenza A (H1N1) vaccine in hemodialysis patients and (2) determine the safety of this vaccine. We conducted a prospective cohort study of 44 hemodialysis patients and 149 healthy controls in 2010. All of the participants received a single dose of the monovalent non-adjuvanted 2009 influenza A (H1N1) vaccine. The level of antibodies was measured at baseline and at 4 and 24 weeks post-vaccination using a hemagglutination inhibition assay. The outcomes were the percentages of participants who achieved seroconversion and seroprotection (titer ≥1:40) 4 and 24 weeks after vaccination. At 4 weeks post-vaccination, seroconversion was observed in 17 (38.6%) of the hemodialysis patients and 94 (63.1%) of the controls (P = 0.056), and protective titers were obtained in 22 (50%) of the hemodialysis patients and 100 (67.1%) of the controls (P = 0.426). At 24 weeks post-vaccination, immunogenicity decreased in both the hemodialysis patients and the controls, but there were no significant differences between the hemodialysis patients and the controls in the seroconversion rate (27.3% versus 36.9%, P = 0.526) or the seroprotection rate (38.6% versus 48.3%, P = 0.996). No differences in adverse events were observed between the hemodialysis patients and the controls. In summary, the 2009 influenza A (H1N1) vaccine elicits a similar immune response in both hemodialysis patients and healthy controls, but immunity declines 24 weeks after vaccination in both groups. Hemodialysis patients should at least be vaccinated annually against the influenza virus.     

55例重症甲型H1N1流感流行特征及预防治疗策略

目的了解浙中西部地区甲型H1N1流感流行特征,为甲型H1N1流感防控提供科学依据。方法分析2009年11月-2010年1月收住医院55例确诊重症甲型H1N1流感病例的临床资料。结果临床主要表现为流感样症状,发热55例,占100.00%,咳嗽52例,占94.55%,涉及多系统、多脏器,少数病例病情进展迅速,出现呼吸衰竭、多脏器功能损伤甚至死亡;94.55%患者出现实验室检查异常;危重症患者病初白细胞数或(和)CRP值明显高于重症患者,差异有统计学意义(P<0.01);55例患者发现肺部炎性改变;53例用磷酸奥司他韦抗病毒治疗;54例治愈,死亡1例。结论儿童、青少年及慢性基础疾病患者和妊娠妇女是甲型H1N1流感和甲型H1N1流感重症的高危人群;发病初期血白细胞和(或)CRP明显升高、淋巴细胞下降者更易发展为危重症,且易误诊误治,应引起临床重视;磷酸奥司他韦加综合治疗,效果可靠;早发现、早治疗是救治成功的关键所在。     

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。     

Development and preclinical testing of HNVAC,a cell culture-based H1N1 pandemic influenza vaccine from India

Several limitations of the use of embryonated eggs and the threat of pandemics have highlighted the need for other platforms for the production of influenza vaccines. We report the indigenous development and pre-clinical testing of an MDCK-based H1N1 pandemic influenza vaccine HNVAC from India. The cell bank and virus seed were characterized extensively. The cells were characterized by PCR, electron microscopy, and karyotyping, and found to be of female canine epithelial origin. The virus was confirmed by neutralization, haemagglutination inhibition, neuraminidase inhibition, and PCR and nucleotide sequencing. Adventitious agent testing was performed by both in vitro and in vivo studies. The in vitro studies included culturing, haemadsorption, haemagglutination, PCR and RT-PCR, whereas in vivo studies included passage in embryonated eggs and in laboratory animals. Both cell bank and virus seed were free of adventitious agents. MDCK cell lysates as well as cellular DNA did not produce tumours in newborn or adult laboratory animals. The bioprocess parameters were standardized to recover antigen with minimal levels of process-related impurities. The vaccine bulk was tested for the presence of specific antigen, and quantified by single radial immunodiffusion. Finally, non-adjuvanted and aluminium hydroxide adjuvanted vaccine formulations were found to be safe in preclinical toxicity studies in mice, rats, guinea pigs and rabbits, and immunogenic in mice and rabbits. This is the first and only cell culture-based influenza vaccine platform developed in any developing country.     

Reduced immune response to influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects

We evaluated the immunogenicity and safety of the influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects. A total of 182 HIV-infected and 42 HIV-uninfected subjects were enrolled, and antibody (ab) titers were measured by hemagglutination-inhibition assay at baseline and 32.3 ± 10.4 and 29.7 ± 3.3 days after vaccination, respectively. In the HIV-infected cohort, ab titers ≥1:40 at baseline and post-vaccination were 12.6% and 49.5%, respectively. The seroconversion rate, defined as either an ab titer ≤1:10 before and ≥1:40 after or ≥1:10 before and ≥4-fold increase in ab titer, was only 38.5% in the HIV-infected cohort, whereas the rate was 85.7% in the HIV-uninfected cohort. Multivariate logistic regression analysis showed that the CD4 cell count was the only significant predictor of a positive vaccine response. There were no serious adverse events in any of the subjects receiving the vaccine. Additional study is warranted to identify a more effective method of vaccinating HIV-infected Japanese subjects.     

2009年甲型H1N1流感疫苗接种影响因素探讨

目的 评价甲型H1N1流感疫苗接种影响因素.方法 采用分层多级抽样的方法,按照距离城区近、中、远的地理位置及人口构成抽取北京市延庆县9个单位参与调查.结果 甲型H1N1流感疫苗接种的影响因素受多方面影响,不同文化程度、接种等待时间、知晓办公地点和时间这三个因素对接种疫苗有影响,经统计学处理,三种因素均对疫苗接种分布的差异有统计学意义(P＜0.05);电视、报纸、网络三种途径共同进行宣传,可以作为今后宣传甲型H1N1流感相关知识工作的重点;政府对甲型H1N1流感疫苗接种的宣传力度合适,占87.04%.结论 延庆县居民对政府优惠接种政策的知晓率较高,但简单地告知并不能提高接种率.