多价钩端螺旋体外膜疫苗的安全性及免疫效果研究

对国内首次研制的多价钩端螺旋体外膜疫苗接种人体安全性和免疫效果进行研究。 10 73名易感青少年随机接种钩端螺旋体三价 (含黄疸出血群赖型、七日热群七日热型、流感伤寒群流感伤寒型 )外膜疫苗、五价 (含黄疸出血群赖型、七日热群七日热型、流感伤寒群流感伤寒型、秋季热群秋季热型、犬群犬型 )外膜疫苗、菌体疫苗和安慰剂 ,分组进行全身和局部的反应观察 ,并以显微镜凝集试验测定各型抗体。结果显示各疫苗组局部和全身反应轻微。三价和五价外膜疫苗免后 1个月和 3个月抗体滴度高于同期相应菌体疫苗诱导的同型抗体滴度 ;且免后 3个月抗体阳转率也较高。提示外膜疫苗较菌体疫苗有更好的免疫原性。     

应对流感大流行的疫苗

最近亚洲暴发的高致病禽流感及相关的人类感染已引起国际社会的高度重视,并意识到必须为可能引起新的流感大流行作好充分准备。首选方法是用疫苗控制流感病毒流行并降低其发病的程度。由于生产减毒活疫苗和灭活流感疫苗的流感病毒疫苗株具有引起流行的可能性,因此借助疫苗种子病毒的研制及其临床前期和临床试验,可以建立原理求证规范,确立必须的生产经验,以防此类病毒扩散进入人群。流感疫苗的研究还能进一步了解禽流感病毒的生物学特征,以及该病毒对哺乳动物宿主所产生的影响。流感大流行除季节性流感外,流感呈周期性大流行,当人类对流感病…     

新疆昌吉州城镇参保职工接种流感疫苗成本效益分析

目的评价新疆昌吉回族自治州城镇参保职工接种流感疫苗的成本效益,为扩大流感疫苗接种工作提供科学依据。方法本次调查以州辖区内城镇参保职工为调查对象,随机抽取1 493名流感疫苗接种者为接种组,选取与接种组性别、年龄、健康状况等相匹配的1 480名未接种疫苗的人为非接种组;对流感相关疾病的就诊率和住院率及医疗费用等进行问卷调查,并对调查结果进行成本-效益分析。结果接种组与非接种组相比,流感相关疾病的就诊率和住院率均明显下降,医疗费用也有不同程度的下降,其中55岁以上人群最为明显;接种流感疫苗控制各类流感相关疾病的效益-成本比(BCR)为6.15。结论新疆昌吉州参保职工接种流感疫苗具有较高的成本效益,产生良好成本效益的原因是明显降低了接种组55岁以上中老年参保职工的就诊率和住院率,从而节省了医疗费用。     

一例甲型H1N1流感疫苗免疫失败的病例报告

2009年4月25日,世界卫生组织（WHO）正式确认新型甲型H1N1流感暴发,疫情快速蔓延,同时甲型H1N1流感疫苗研发工作也在全球迅速展开,中国最早完成甲型H1N1流感疫苗临床试验,山东省9月22日开始接种疫苗。11月9日,山东省疾病预防控制中心接到一例接种甲型H1N1流感疫苗病例后发热、咽痛、咳嗽伴全身酸痛等典型流感样症状的病例报告,     

广州地区2009年甲型H1N1流行性感冒疫情自然免疫血清抗体调查

据世界卫生组织(WHO)2010年2月初报告估计,全球共接种甲型H1N1流行性感冒(流感)疫苗1.75亿剂次.截至2010年3月9日24时,我国食品药品监督管理局累计完成批签发732批次13 786.1万人份流感疫苗.全国31个省(区、市)、新疆生产建设兵团累计签收疫苗10 485万人份,累计完成接种8217万人[1].在注射疫苗前,接种人群的背景调查至关重要[2],需尽可能排除疫苗带来的不良反应,特别是一些对疫苗接种有禁忌和顾虑的人群.在这类未接种人群中,甲型H1N1流感抗体阳性人群更是不需接种的对象.进行自然免疫血清抗体的摸底调查,排除自然免疫人群的接种,能避免重复免疫,节约社会资源;同时为开展疫苗接种前的抗体水平检测的必要性提供数据支持.     

流感通用疫苗的研究进展

流感是一种呼吸道传染性疾病.目前制备流感疫苗主要利用流感病毒的HA和NA诱导相应的抗体,但存在抗原漂移和抗原转换等问题.解决办法之一就是研制流感通用疫苗.M2e是流感病毒M2蛋白的胞外区,它的序列相对保守.利用HBc作为病毒样颗粒包装M2e是至今为止制备流感通用疫苗最可行的方法.实验证明,M2e-HBc融合蛋白不仅能诱导出足够的抗体,还能增强T细胞反应,产生交叉性保护效应,大大降低流感病毒的致病率、致死率,促进疾病的恢复.此外,还有流感病毒的NP和HA等保守序列,结合佐剂及黏膜给药方式都不失为通用疫苗的可行选择.     

成都市金牛区健康人群甲型H1N1流感抗体水平监测及疫苗免疫效果分析

了解成都市金牛区健康人群甲型H1N1流感抗体水平和甲型H1N1流感疫苗的免疫效果。方法分别于一个流行期前后检测3~11、12~17、18~60、60岁4个年龄组健康人群甲型H1N1流感抗体水平,同时对部分人群分年龄组接种甲型H1N1流感疫苗,1月后检测其抗体水平。结果目前该区健康人群甲型H1N1流感抗体达到保护水平的比例为44.23%,GMT水平为1∶23.35,各年龄组差异有统计学意义(χ2=46.42,P0.01;F=25.02,P0.01),其中3~11、12~17岁组抗体水平较流行前期均有上升;甲型H1N1流感疫苗免疫后人群抗体阳转率为88.98%,GMT水平为1∶325.20,各年龄组之间差异有统计学意义(χ2=23.78,P0.01;F=13.23,P0.01),以311岁组水平较低。结论目前除1217岁组抗体水平较高外,其他年龄组保护性抗体比例仍较低,有必要对其继续加强甲型H1N1流感疫苗的宣传和接种。     

像对待婴幼儿一样对待自己——糖友应做好疫苗接种

大家都知道,小孩从出生开始就要接种一系列的疫苗,值得称赞的是,我国从几年前就开始免费接种.您知道吗？糖尿病患者同样需要接种疫苗,这是因为糖尿病患者更容易被传染,而且患上流感或肺炎后更容易发生并发症.目前,我国一些地区已经开始为老年人免费接种流感疫苗,很多地区也已经把疫苗接种费用纳入了医保报销范畴,上海市去年还开始为沪籍老年人免费接种肺炎疫苗,这些都是非常好的医改措施.     

休斯敦市享受公费医疗的HIV感染者肺炎疫苗、流感疫苗接种情况

目的 研究休斯敦市近年享受公费医疗的艾滋病病毒（HIV）感染者接种肺炎疫苗和流感疫苗的水平,分析影响疫苗接种的因素,为中国提供参考。方法 使用休斯敦市公共卫生服务局“成人和青少年HIV／AIDS长期监测项目”的有关数据,采用多重回归分析方法,分析肺炎疫苗和流感疫苗接种是否与患者的年龄、性别、种族、感染途径、CD4细胞数量和看病次数相关。结果 2000和2001年,在休斯敦公立医院首次就诊的562名HIV感染者的肺炎疫苗和流感疫苗接种率分别为37．2％和28．5％。两种疫苗接种情况与患者年龄、性别、种族、感染途径、CD4细胞数量无关;但与病人看病次数相关。结论 HIV感染者接种肺炎疫苗和流感疫苗的水平偏低,可能是由医生、病人以及医疗服务体系多方面因素造成。     

美国《Emerging Infectious Diseases》2006年第1期有关人兽共患病论文摘译

流感再肆虐；H5NI型禽流感爆发与动物性流感；应对流感大流行的疫苗；流感大流行；禽类是流感大流行的病毒储存宿主；开发应对大流行的流感疫苗     

Influenza season triggers pneumococcal vaccination

OBJECTIVES: To investigate the frequency with which influenza and pneumococcal vaccines are administered alone and together. DESIGN: Retrospective review. SETTING: Marshall University internal medicine practice, Huntington, West Virginia. PARTICIPANTS: All patients aged 65 and older seen in the practice from 1999 through 2005 who received pneumococcal or influenza vaccine. MEASUREMENTS: Billing records were reviewed for administration of pneumococcal and influenza vaccines to Medicare beneficiaries, and rates of administration of these vaccines given alone and together were calculated. RESULTS: Nine hundred sixty-nine doses of pneumococcal vaccine were administered. Of these, 796 (82%) were administered during the fall and winter. Three hundred fifty-six (45%) pneumococcal vaccinees received it together with influenza vaccine. During 2001 and 2005, when influenza vaccine supply was limited, the rate of pneumococcal vaccine administered together with influenza vaccine declined sharply. Nonetheless, the rate of pneumococcal vaccination remained relatively stable because of an increase in the rate of vaccine administered alone. CONCLUSION: Four-fifths of pneumococcal vaccine was administered in the fall and winter, and approximately half was given together with influenza vaccine. When influenza vaccine was in limited supply, physicians continued to vaccinate with pneumococcal vaccine alone. These findings suggest that the imminent influenza season provides the trigger for physicians to prescribe pneumococcal vaccine. Physicians should be reminded that pneumococcal vaccine can be administered any time of year.     

An overview of the regulation of influenza vaccines in the United States

Influenza virus vaccines are unique among currently licensed viral vaccines. The vaccines designed to protect against seasonal influenza illness must be updated periodically in an effort to match the vaccine strain with currently circulating viruses, and the vaccine manufacturing timeline includes multiple, overlapping processes with a very limited amount of flexibility. In the United States (U.S.), over 150 million doses of seasonal trivalent and quadrivalent vaccine are produced annually, a mammoth effort, particularly in the context of a vaccine with components that usually change on a yearly basis. In addition, emergence of an influenza virus containing an HA subtype that has not recently circulated in humans is an ever present possibility. Recently, pandemic influenza vaccines have been licensed, and the pathways for licensure of pandemic vaccines and subsequent strain updating have been defined. Thus, there are formidable challenges for the regulation of currently licensed influenza vaccines, as well as for the regulation of influenza vaccines under development. This review describes the process of licensing influenza vaccines in the U.S., the process and steps involved in the annual updating of seasonal influenza vaccines, and some recent experiences and regulatory challenges faced in development and evaluation of novel influenza vaccines.     

Virus-Vectored Influenza Virus Vaccines

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines.     

Universal Live-Attenuated Influenza Vaccine Candidates Expressing Multiple M2e Epitopes Protect Ferrets against a High-Dose Heterologous Virus Challenge

The development of an influenza vaccine with broad protection and durability remains an attractive idea due to the high mutation rate of the influenza virus. An extracellular domain of Matrix 2 protein (M2e) is among the most attractive target for the universal influenza vaccine owing to its high conservancy rate. Here, we generated two recombinant live attenuated influenza vaccine (LAIV) candidates encoding four M2e epitopes representing consensus sequences of human, avian and swine influenza viruses, and studied them in a preclinical ferret model. Both LAIV+4M2e viruses induced higher levels of M2e-specific antibodies compared to the control LAIV strain, with the LAIV/HA+4M2e candidate being significantly more immunogenic than the LAIV/NS+4M2e counterpart. A high-dose heterosubtypic influenza virus challenge revealed the highest degree of protection after immunization with LAIV/HA+4M2e strain, followed by the NS-modified LAIV and the classical LAIV virus. Furthermore, only the immune sera from the LAIV/HA+4M2e-immunized ferrets protected mice from a panel of lethal influenza viruses encoding M genes of various origins. These data suggest that the improved cross-protection of the LAIV/HA+4M2e universal influenza vaccine candidate was mediated by the M2e-targeted antibodies. Taking into account the safety profile and improved cross-protective potential, the LAIV/HA+4M2e vaccine warrants its further evaluation in a phase I clinical trial.     

Options and Obstacles for Designing a Universal Influenza Vaccine

Since the discovery of antibodies specific to a highly conserved stalk region of the influenza virus hemagglutinin (HA), eliciting such antibodies has been considered the key to developing a universal influenza vaccine that confers broad-spectrum protection against various influenza subtypes. To achieve this goal, a prime/boost immunization strategy has been heralded to redirect host immune responses from the variable globular head domain to the conserved stalk domain of HA. While this approach has been successful in eliciting cross-reactive antibodies against the HA stalk domain, protective efficacy remains relatively poor due to the low immunogenicity of the domain, and the cross-reactivity was only within the same group, rather than among different groups. Additionally, concerns are raised on the possibility of vaccine-associated enhancement of viral infection and whether multiple boost immunization protocols would be considered practical from a clinical standpoint. Live attenuated vaccine hitherto remains unexplored, but is expected to serve as an alternative approach, considering its superior cross-reactivity. This review summarizes recent advancements in the HA stalk-based universal influenza vaccines, discusses the pros and cons of these approaches with respect to the potentially beneficial and harmful effects of neutralizing and non-neutralizing antibodies, and suggests future guidelines towards the design of a truly protective universal influenza vaccine.     

A Glycolipid α-GalCer Derivative, 7DW8-5 as a Novel Mucosal Adjuvant for the Split Inactivated Influenza Vaccine

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, with the withdrawal of cholera toxin and Escherichia coli heat-labile endotoxin from clinical use due to side effects, there are no approved adjuvants for intranasal vaccines. Therefore, safe and effective mucosal adjuvants are urgently needed. Previously, we reported that one derivative of α-Galactosylceramide (α-GalCer), 7DW8-5, could enhance the protective efficacy of split influenza vaccine by injection administration. However, the mucosal adjuvanticity of 7DW8-5 is still unclear. In this study, we found that 7DW8-5 promotes the production of secret IgA antibodies and IgG antibodies and enhances the protective efficacy of the split influenza vaccine by intranasal administration. Furthermore, co-administration of 7DW8-5 with the split influenza vaccine significantly reduces the virus shedding in the upper and lower respiratory tract after lethal challenge. Our results demonstrate that 7DW8-5 is a novel mucosal adjuvant for the split influenza vaccine.     

T Cell Immunity against Influenza: The Long Way from Animal Models Towards a Real-Life Universal Flu Vaccine

Current flu vaccines rely on the induction of strain-specific neutralizing antibodies, which leaves the population vulnerable to drifted seasonal or newly emerged pandemic strains. Therefore, universal flu vaccine approaches that induce broad immunity against conserved parts of influenza have top priority in research. Cross-reactive T cell responses, especially tissue-resident memory T cells in the respiratory tract, provide efficient heterologous immunity, and must therefore be a key component of universal flu vaccines. Here, we review recent findings about T cell-based flu immunity, with an emphasis on tissue-resident memory T cells in the respiratory tract of humans and different animal models. Furthermore, we provide an update on preclinical and clinical studies evaluating T cell-evoking flu vaccines, and discuss the implementation of T cell immunity in real-life vaccine policies.     

Targeting Antigens for Universal Influenza Vaccine Development

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.     

Improving influenza vaccine virus selection: report of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June 2010

? For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. ? The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy-making community of the complexity of influenza vaccine virus selection. ? The selection process is highly coordinated and involves continual year-round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). ? Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non-antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. ? Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. ? Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. ? Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays - for example based upon advanced recombinant DNA and protein technologies - may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. ? Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large-scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. ? Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well-characterized banks of age-stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. ? Advances in high-throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X-ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. ? Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non-mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. ? The adoption of alternative vaccine technologies - such as live-attenuated, quadrivalent or non-HA-based vaccines - has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high-growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. ? The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.     

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross‐reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13–23. Background Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross‐reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were immunised by particle‐mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses. Results We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross‐reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross‐reactive immune responses against a recent 2005 H3N2 virus challenge. Conclusions DNA vaccines based on pandemic or recent seasonal influenza genes induced cross‐reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross‐protective immunity against both contemporary and long‐time drifted viruses.