Efficacy of Influenza A H1N1/2009 Vaccine in Hemodialysis and Kidney Transplant Patients

Summary

Background and objectives

Data are needed to assess safety and efficacy of the 2009 pandemic influenza A H1N1 vaccine in renal patients.

Design, setting, participants, & measurements

We prospectively evaluated seroconversion, predictors of response, and vaccine safety in renal patients. Hemagglutination inhibition tests to detect serum antibodies against a new influenza A-H1N1 virus were performed in 79 transplant patients, 48 hemodialysis patients, and 15 healthy workers before and 1 month after vaccination. Healthy controls and 88 of 127 renal patients were vaccinated. Seroconversion was defined as at least 2 dilutions increase in titer.

Results

We excluded 19 individuals seroprotected (≥1/40) against the novel H1N1 in the initial sample. Efficacy rate in the 96 vaccinated individuals was 43.7% (42 of 96 seroconverted versus four of 27 nonvaccinated patients, P = 0.007). For vaccinated subgroups, efficacy was 41.8% in transplant patients (P = 0.039 versus nonvaccinated), 33.3% in hemodialysis patients (P = 0.450), and 81.8% in controls. Healthy controls showed better response to vaccine than transplant (P = 0.021) and dialysis (P = 0.012) patients. For the transplant subgroup, longer time after transplantation (P = 0.028) was associated with seroconversion, but no influence was found for age, gender, renal function, or immunosuppression. In the hemodialysis subgroup, younger age was associated with response (55.7 ± 20.8 versus 71.6 ± 10.1 years, P = 0.042), but other specific variables, including Kt/V or time on dialysis, were not. No serious adverse events were reported, and kidney function was stable.

Conclusion

The novel influenza A 2009 H1N1 vaccine was safe in renal patients, although administration of a single dose of adjuvanted vaccine induced a poor response in these patients.     

Characterization and Immunogenicity of Influenza H7N9 Vaccine Antigens Produced Using a Serum-Free Suspension MDCK Cell-Based Platform

Human infections with avian-origin H7N9 influenza A viruses were first reported in China, and an approximately 38% human mortality rate was described across six waves from February 2013 to September 2018. Vaccination is one of the most cost-effective ways to reduce morbidity and mortality during influenza epidemics and pandemics. Egg-based platforms for the production of influenza vaccines are labor-intensive and unable to meet the surging demand during pandemics. Therefore, cell culture-based technology is becoming the alternative strategy for producing influenza vaccines. The current influenza H7N9 vaccine virus (NIBRG-268), a reassortant virus from A/Anhui/1/2013 (H7N9) and egg-adapted A/PR/8/34 (H1N1) viruses, could grow efficiently in embryonated eggs but not mammalian cells. Moreover, a freezing-dry formulation of influenza H7N9 vaccines with long-term stability will be desirable for pandemic preparedness, as the occurrence of influenza H7N9 pandemics is not predictable. In this study, we adapted a serum-free anchorage-independent suspension Madin-Darby Canine Kidney (MDCK) cell line for producing influenza H7N9 vaccines and compared the biochemical characteristics and immunogenicity of three influenza H7N9 vaccine antigens produced using the suspension MDCK cell-based platform without freeze-drying (S-WO-H7N9), the suspension MDCK cell-based platform with freeze-drying (S-W-H7N9) or the egg-based platform with freeze-drying (E-W-H7N9). We demonstrated these three vaccine antigens have comparable biochemical characteristics. In addition, these three vaccine antigens induced robust and comparable neutralizing antibody (NT; geometric mean between 1016 and 4064) and hemagglutinin-inhibition antibody (HI; geometric mean between 640 and 1613) titers in mice. In conclusion, the serum-free suspension MDCK cell-derived freeze-dried influenza H7N9 vaccine is highly immunogenic in mice, and clinical development is warranted.     

Safety and Immunogenicity of a Rederived,Live-Attenuated Dengue Virus Vaccine in Healthy Adults Living in Thailand: A Randomized Trial

Safety and immunogenicity of two formulations of a live-attenuated tetravalent dengue virus (TDEN) vaccine produced using rederived master seeds from a precursor vaccine were tested against a placebo control in a phase II, randomized, double blind trial ({"type":"clinical-trial","attrs":{"text":"NCT00370682","term_id":"NCT00370682"}}NCT00370682). Two doses were administered 6 months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and 97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and signs reported after vaccination were mild to moderate and transient. There were no vaccine-related serious adverse events or dengue cases reported. Asymptomatic, low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of flavivirus-primed subjects were seropositive to antibodies against all four DENV types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an acceptable safety profile in flavivirus-primed adults.     

甲型H1N1流感疫苗血清抗体消长研究

目的 了解甲型H1N1流感疫苗接种后血清抗体的消长规律,为免疫策略提供依据。方法 对128名接种甲型H1N1流感疫苗的研究对象在接种后的第3、6、9、12个月采集血清标本,以血凝抑制试验方法(HI)检测血清HI抗体。结果 128名对象在接种疫苗后的第3、6、9、12个月抗体阳性率和几何平均滴度(GMT)分别为61.7%和1:40;47.7%和1:28.4;40.9% 和1:24.5;35.43% 和1:23.6,差异有显著统计学意义（P<0.01）。不论男女,抗体阳性率和GMT均随时间推移显著降低（P<0.01）。不同年龄组的抗体GMT也显著下降（P<0.01）。79名抗体阳性者在第3、6、9、12个月的抗体阳性率和GMT分别为100%和1:104.09;75.95%和1:58.33;64.56%和1:45.23;54.43%和1:41.82,差异有显著统计学意义（P<0.01）。无论性别或年龄,抗体阳性率和GMT均随时间推移显著降低（P<0.01）。结论 甲型H1N1流感疫苗的血清抗体水平随时间推移快速下降,免疫力不持久。     

Safety and Immune Responses in Children After Concurrent or Sequential 2009 H1N1 and 2009-2010 Seasonal Trivalent Influenza Vaccinations

Background.?Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Methods.?Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results.?All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Conclusions.?Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. Clinical Trials Registration.?NCT00943202.     

Low transmission rate of 2009 H1N1 Influenza during a long-distance bus trip

Background  

Current data on the risk of transmission of 2009 H1N1 Influenza in public transportation systems (e.g., public trains, busses, airplanes) are conflicting. The main transmission route of this virus is thought to be via droplets, but airborne transmission has not been completely ruled out.     

H1N1 Influenza Pandemic of 2009 Compared With Other Influenza Pandemics: Epidemiology,Diagnosis, Management,Pulmonary Complications,and Outcomes

Influenza pandemics are complex events that have occurred frequently throughout human history, three during the past century alone. Now the world is facing the first 21st century pandemic, and the comparison among them is essential to identify common epidemiologic patterns, clinical characteristics, and outcomes. The evolution of medicine, including diagnostic and treatment options, the critical care advances, and global responses are new interventions that could modify the general outcome of the pandemic. Learning from past and current events could lead to a plan for prompt and efficient response in future pandemics and may be help us to predict the unpredictable.     

2009年湖北省甲型H1N1流感重症病例60例临床分析

目的：分析湖北省甲型H1N1流感重症病例的临床特点。方法对2009年11月～2010年1月湖北省各医院收治的60例甲型H1N1流感确诊病例的临床特点进行回顾性分析。结果：60例患者中重症37例,危重症23例。女性占55.0%,其中57.6%为孕产妇。年龄2～62岁,中位年龄25岁。98.3%的患者有发热,其它症状有咳嗽（95.0%）、咳痰（68.3%）、呼吸困难（60.0%）、全身症状（60.0%）、上呼吸道感染症状（55.0%）、神经系统症状（33.3%）、消化系统症状（21.7%）、咯血（16.7%）、胸痛（3.3%）。体检：咽部充血（73.3%）、扁桃体肿大（31.7%）、紫绀（36.7%）、肺部罗音（65.0%）。实验室检查：70.0%的患者中性粒细胞比例升高,68.3%淋巴细胞比率降低。AST升高（57.9%）,LDH升高（61.2%）,CK升高（50.0%）,血沉增快（63.6%）,C反应蛋白升高（94.1%）。部分伴ALT、ALP、TBIL、cTnI、Cr升高及低钾、低钠血症,或凝血功能异常。59例接受奥司他韦抗病毒治疗。36例需重症监护,其中13例使用有创机械通气,7例使用无创机械通气。死亡7例,其中4例为孕妇。结论：甲型H1N1流感重症患者以青壮年居多,孕产妇所占比例较大、病死率较高。应早期识别和行奥司他韦抗病毒以及多器官功能支持治疗,孕产妇需高度重视。     

A Phase II,Randomized, Safety and Immunogenicity Trial of a Re-Derived,Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico

This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1–50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2–4 years], 60% [5–20 years], and 93% [21–50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00468858","term_id":"NCT00468858"}}NCT00468858.     

Community knowledge,behaviours and attitudes about the 2009 H1N1 Influenza pandemic: a systematic review

Background

Effectiveness of pandemic plans and community compliance was extensively researched following the H1N1 pandemic. This systematic review examined community response studies to determine whether behavioural responses to the pandemic were related to level of knowledge about the pandemic, perceived severity of the pandemic and level of concern about the pandemic.

Methods

Literature databases were searched from March 2009 to August 2011 and included cross‐sectional or repeated population surveys undertaken during or following the H1N1 pandemic which reported on community response to the pandemic. Studies using population subgroups and other respiratory diseases were excluded, as were mathematical modelling and qualitative studies.

Results

Nineteen unique studies were included. Fourteen reported pandemic knowledge, 14 reported levels of concern and risk perception and 18 reported pandemic behaviours. Awareness of the pandemic was high, and knowledge was moderate. Levels of concern and risk were low moderate and precautionary behavioural actions lower than intentions. The most commonly reported factors influencing adopting recommended behaviours were increased risk perception and older age, increased pandemic knowledge and being female.

Conclusions

Important implications for future pandemic planning were identified. A remarkable lack of intercountry variability in responses existed; however, differences between populations within a single country suggest one‐size‐fits‐all plans may be ineffective. Secondly, differences between reported precautionary intentions and preventive behaviours undertaken may be related to people''s perceived risk of infection.     

Safety and Immunogenicity of a Dengue Virus Serotype-1 Purified-Inactivated Vaccine: Results of a Phase 1 Clinical Trial

We describe the results from a human clinical trial of a dengue virus serotype-1, purified-inactivated vaccine (DENV-1 PIV) adjuvanted with aluminum hydroxide. This first-in-man, Phase 1, open-label clinical trial consisted of two groups of flavivirus-naïve healthy adult volunteers that received two intramuscular vaccine doses of either 2.5 μg or 5 μg of DENV-1 PIV administered on days 0 and 28. Following vaccination, both vaccine doses exhibited an acceptable safety profile with minimal injection site and systemic reactions. By study day 42, 2 weeks following the second vaccine dose, all volunteers in both vaccine groups developed serum-neutralizing antibodies against DENV-1. Additional testing using an enzyme-linked immunosorbent assay demonstrated induction of a humoral immune response following both vaccine doses. The DENV-1 PIV was safe and immunogenic in a small number of volunteers supporting development and further testing of a tetravalent DENV PIV formulation.