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.     

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.     

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。     

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.     

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。     

青海省首例甲型H1N1流感病例的实验室检测

目的 青海省疾控中心流感网络实验室利用中国疾控中心病毒病所国家流感中心统一配发的引物探针对青海省一例输入性疑似甲型H1N1流感病例的临床鼻咽双拭子标本进行检测.方法 采用Real-time PCR和RT-PCR两种方法进行检测.结果 临床鼻咽双拭子标本经检测为甲型H1N1流感病毒核酸阳性.结论 该疑似甲型H1N1流感病例成为青海省首例确诊的甲型HIN1流感病例.     

Pandemic influenza A H1N1 vaccine in recipients of solid organ transplants: immunogenicity and tolerability outcomes after vero cell derived, non-adjuvanted, whole-virion vaccination

During the 2009/10 pandemic of influenza A (H1N1), the American Society of Transplantation and other health organizations recommended that immunocompromised patients should be vaccinated as the key preventive measure. Since there are no data available for the immunogenicity of the unadjuvanted pandemic influenza vaccine in immunocompromised patients - as opposed to the adjuvanted preparation - the objective of this study was to evaluate the immunogenicity of an adjuvant-free H1N1 vaccine in recipients of solid organ transplants. Patients were recruited at the Vienna General Hospital, Austria. The vaccination schedule consisted of 2 doses of a whole-virion, vero cell derived, inactivated, non-adjuvanted influenza A/California/07/2009 (H1N1) vaccine given with an interval of 3 weeks. A hemagglutination inhibition (HI) assay on blood samples obtained prior to the first and after each vaccination was used for serologic analysis. The primary immunologic endpoint was the seroconversion rate, defined as the proportion of subjects with an individual 4-fold increase in HI titer of at least 1:40. In addition, virus-specific IgG antibodies to the pandemic H1N1 strain were measured using a commercially available ELISA.Twenty-five organ transplant patients (16 males, 9 females) aged 25-79 years were vaccinated and provided blood samples for serologic analysis. The time elapsed since transplantation was 10 months to 25 years (mean: 9 years; 95% CI 6-13 years). The vaccine was well tolerated and no local adverse events were noticed. After two vaccinations 37% of the patients demonstrated seroconversion in the HI assay as defined above and 70% had virus-specific IgG antibodies. Among the HI vaccine responders were 6 of 14 heart transplant recipients and 1 of 4 liver transplant recipients. The number and type of immunosuppressive agents did not significantly differ in their effect on the immune response.Our results show that the novel vero cell derived and adjuvant-free pandemic A/California/07/2009 (H1N1) influenza vaccine induced limited but measurable immune responses in adult recipients of solid organ transplants.     

淄博市甲型H1N1流感感染状况的调查

目的了解淄博市不同人群甲型H1N1流感实际感染水平和动态变化趋势,为应对流感大流行,完善防控措施提供可靠依据。方法 2010年1月～9月期间,采取多阶段随机抽样方法抽取4500名调查对象,进行问卷调查,并采集血清利用血凝抑制方法检测甲型H1N1流感抗体水平。结果该市甲型H1N1流感病毒抗体阳性率为25.60%,自然感染率为21.09%,显性感染和隐性感染比例为1.97︰1;抗体阳性率以16～24和6～15岁年龄组最高,60岁以上年龄组最低;教师和学生阳性率最高,医务人员阳性率相对较低;第1次调查抗体阳性率最高,第3次调查最低,接种甲型H1N1流感疫苗半年后抗体阳性率为11.36%。结论甲型H1N1流感大流行期间,该市实际感染人数远远超过确诊病例数,学龄人群和年轻人是最大的感染群体,人群中存在无症状感染者,自然感染或接种疫苗后抗体水平随时间推移逐步下降。     

Immune response after one or two doses of pandemic influenza A (H1N1) monovalent,AS03-adjuvanted vaccine in HIV infected adults

Introduction

Continued research is needed to evaluate and improve the immunogenicity of influenza vaccines in HIV infected patients. We aimed to determine the antibody responses after one or two doses of the AS03-adjuvanted pandemic influenza A (H1N1) vaccine in HIV infected patients.

Method

Following the influenza season 2009/2010, 219 HIV infected patients were included and divided into three groups depending on whether they received none (n = 60), one (n = 31) or two (n = 128) doses of pandemic influenza A (H1N1) vaccine. At inclusion, antibody titers for all patients were analyzed and compared to pre-pandemic antibody titers analyzed from serum samples in a local storage facility.

Results

4–9 months after a single immunization, we found a seroprotection rate of 77.4% and seroconversion rate of 67.7%. After two immunizations the rates increased significantly to seroprotection rate of 97.7% and seroconversion rate of 86.7%.

Conclusion

A single dose of AS03-adjuvanted pandemic influenza A (H1N1) vaccine created an adequate immune response in HIV infected patients lasting as long as 4–9 months. Two doses improved the immunogenicity further.     

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.     

Antigenic stability of H1N1 pandemic vaccines correlates with vaccine strain

In 2009 a novel H1N1 influenza virus emerged and spread rapidly. Soon after vaccine lots were released, however, the shelf life was revised downward due to an unexpected decrease in HA potency. In this study, we found differences in both stability and antigenic content of two monovalent H1N1/2009 vaccine preparations. These appear to have arisen due to differences in the A/California/7/2009-like influenza strain used to prepare vaccine.     

Durability of antibody responses after receipt of the monovalent 2009 pandemic influenza A (H1N1) vaccine among HIV-infected and HIV-uninfected adults

Background

Human immunodeficiency virus (HIV)-infected persons are at risk for severe influenza infections. Although vaccination against the H1N1 pandemic influenza strain is recommended, currently there are no data on the durability of post-vaccination antibody responses in this population.

Methods

HIV-infected and HIV-uninfected adults (18-50 years old) received a single dose of monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1). Antibody levels to the 2009 H1N1 pandemic strain were determined at day 0, day 28, and 6 months by hemagglutination-inhibition assay. A seroprotective response was a post-vaccination titer of ≥1:40 among those with a pre-vaccination level of ≤1:10. Geometric mean titers (GMT) and factors associated with higher levels were also evaluated.

Results

We studied 127 participants with a median age of 35 (interquartile range (IQR) 28, 42) years. Among the HIV-infected arm (n = 63), the median CD4 count was 595 (IQR 476, 819) cells/mm³ and 83% were receiving HAART. Thirty-five percent of all participants had a pre-vaccination level of >1:10. HIV-infected compared to HIV-uninfected adults were less likely to generate a seroprotective response at day 28 (54% vs. 75%, adjusted OR 0.23, p = 0.021) or have a durable response at 6 months post-vaccination (28% vs. 56%, adjusted OR 0.19, p = 0.005). Additionally, although pre-vaccination GMT were similar in both arms (median 7 vs. 8, p = 0.11), the GMT at 6 months was significantly lower among HIV-infected versus HIV-uninfected adults (median 20 vs. 113, p = 0.003). Among HIV-infected persons, younger age (p = 0.035) and receipt of HAART (p = 0.028) were associated with higher GMTs at 6 months.

Conclusions

Despite vaccination, most HIV-infected adults do not generate durable seroprotective antibody responses to the 2009 influenza A (H1N1) virus, and hence may remain vulnerable to infection. In addition to HAART use, more immunogenic vaccines are likely needed for improving protection against influenza in this population.     

Immunogenicity and safety of inactivated monovalent 2009 H1N1 influenza A vaccine in immunocompromised children and young adults

Background

Influenza vaccination is recommended for immunocompromised patients.

Methods

Children (6 months to 21 years) with cancer, HIV infection, or sickle cell disease (SCD) received 1 or 2 doses of pandemic 2009 H1N1 monovalent influenza vaccine (H1N1 MIV). Safety and tolerability, hemagglutination inhibition (HI) and microneutralization (MN) antibody titers were measured against 2009 H1N1 influenza A virus after each dose. Seroprotection (SP) and seroconversion (SC) rates were determined.

Results

103 participants were enrolled and 99 were evaluable (39 with HIV, 37 with cancer and 23 with SCD). Mean age (±SD) was 7.9 (±5.4) years for cancer participants, 18.0 (±3.5) for HIV, and 13.3 (±4.2) for SCD. 54% were males; 65% black; and 96% had received seasonal influenza vaccine. HIV-infected participants had a median CD4 count of 625 cells/mm³ (range, 140-1260). 46% had an undetectable HIV viral load and 41% were perinatally infected. No participant had vaccine-related serious adverse events. None developed influenza A proven illness during the 6 months after the vaccine. Local injection reactions were reported in 29% and systemic reactions in 42% after the first dose of vaccine. SC and SP were achieved after the last dose in 48% and 52%, respectively, of participants with leukemia or lymphoma, 50% and 75% of participants with solid tumors, 63% and 92% of HIV-infected participants, and 74% and 100% of participants with SCD.

Conclusion

H1N1 MIV was safe and well tolerated. H1N1 MIV resulted in an adequate immune response in children with SCD. It was only modestly immunogenic in cancer or HIV participants.     

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.     

Improved neutralizing antibody response in the second season after a single dose of pandemic (H1N1) 2009 influenza vaccine in HIV-1-positive adults

Neutralizing antibody titers were determined before and after a single dose of pandemic (H1N1) 2009 influenza vaccine in HIV-1-positive Japanese adults in the first season of the pandemic and in those in the second season who had already received the vaccine in the first season. The antibody response rate at 2-month post-vaccination increased significantly from 49.0% (50/102, 95%CI: 39.0-59.1%) in the 2009/2010 season to 66.7% (42/63, 95%CI: 53.7-78.1%) in the 2010/2011 season. Geometric mean antibody titers (fold dilution) at baseline, at 2 months, and at 4 months also increased significantly from 4.4 (95%CI: 3.3-5.7), 19.0 (95%CI: 13.4-26.8) and 13.7 (95%CI: 9.3-20.2), respectively, in the 2009/2010 season to 8.3 (95%CI: 5.8-11.7), 47.0 (95%CI: 32.2-68.6) and 38.2 (95%CI: 23.8-61.4), respectively, in the 2010/2011 season. Although the vaccine response was low in the first season, it was improved in the second season.     

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。     

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...     

2009-2010年浙江省人群甲型H1N1流感抗体水平调查分析

目的了解2009-2010年浙江省人群甲型H1N1流感抗体水平。方法每次调查在医院中非流感样病例就诊者、健康体检者和到血液中心的献血者共400人,并采集他们的血液样本5 ml/人,共调查5次。结果本研究共调查2 003人,甲型H1N1流感抗体阳性402人,阳性率20.07%。5次调查的抗体阳性率不同,随着时间的推移,抗体阳性率呈升高趋势。经统计学检验差异有统计学意义(χ2=69.072,P<0.01)。结论甲型H1N1流感是一种新型流感,人群的免疫力普遍较低。甲型H1N1流感疫苗的保护作用良好。但本次调查结果具有一定程度的偏倚,不能够完全地代表全人群的抗体阳性率水平。