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…     

疫苗保护小鼠免遣多种H5N1型禽流感病毒侵袭

据Medscape．com 2月1日报道（原载Lancet 2006），美国研究已经研制了一种依赖腺病毒载体的疫苗可用来有效地预防禽流感，与过去的同类疫苗相比，它具有多种优点，包括易于大规模生产和可针对不同抗原型的H5N1禽流感病毒株产生保护功效。对高致病性H5N1型禽流感病毒在人与人之间传播可能会造成流感大流行的惧怕反而刺激了人们努力去研制一种新的预防此病毒的疫苗。以前的此类疫苗都是依赖受精鸡胚生产的减毒疫苗。     

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     

磷酸奥司他韦治疗流行性感冒的进展

流行性感冒 (以下简称流感 )是由一种正黏病毒漯科病毒引起的急性呼吸道疾病 ,该病毒有三种类型 ,Ａ型、Ｂ型和Ｃ型流感病毒。Ａ型和Ｂ型流感病毒可引起呼吸道急性发热性感染 ,特点为突然出现发热、不适、头痛、肌痛和咳嗽等症状。虽然这种感染一般属于自限性疾病 ,但在儿童、老年和免疫力低下者 ,可引起死亡。在美国 ,估计每年有 2 0 0 0 0人死于流感。近年来出现了一些针对流感的新药和疫苗 ,但死于流感的人数并无下降。 1994年由ＧｉｌｅａｄＳｃｉｅｎｃｅｓ和Ｈｏｆｆｍａｎｎ ＬａＲｏｃｈｅ共同研制出了用于治疗和预防流感的一种新药…     

北京市某高校甲型H1N1流行性感冒裂解疫苗接种效果分析

2009年一场由新型甲型H1N1流行性感冒(流感)病毒引起的流感疫情在墨西哥暴发,并迅速在多个国家和地区蔓延[1].它引起的临床症状与季节性流感相似,但传染性强于季节性流感病毒,极易在学校、社区暴发流行.研究表明,流感疫苗接种是预防和控制流感最有效的方法[2].本研究分析接种疫苗和未接种的两组学生在历时25 d流感疫情暴发阶段患病情况,旨在了解甲型H1N1流感疫苗对易感人群的保护作用.     

拉沙热疫苗研究进展

拉沙热是由拉沙病毒(Lassa virus, LASV)引起的一种急性传染病,主要由啮齿类动物传给人. 西非是拉沙热最主要的流行区,该地区每年有几十万人患病,数千例死亡.由于LASV的高致病性,被列为潜在生物战剂,当前无获批的拉沙热疫苗.研究表明传统的灭活疫苗免疫保护效果不理想,LASV基因重组的复制增殖型病毒载体疫苗、复制缺陷型病毒载体疫苗和DNA疫苗等新型疫苗显示较好的发展前景. 但是这几种新型疫苗仍处于临床预试验阶段或临床试验阶段.     

以人乳头瘤病毒16 L1为载体的流感通用疫苗初步研究

目的 构建以人乳头瘤病毒(human papillomavirus,HPV)16 L1为载体的甲型流感病毒M2基因胞外区(M2e)通用疫苗杆粒,利用昆虫细胞杆状病毒表达系统,进行初步的蛋白表达.方法 利用PCR技术将甲型流感病毒M2e基因序列与HPVl6 L1相连.经酶切、酶联将融合基因插入pFastBacHTA载体,在DH10Bac细胞中进行同源重组,经测序鉴定后构建M2e-HPV16 L1杆粒,脂质体转染sf9昆虫细胞,收获并扩增含有M2e-HPV16 L1的杆状病毒,经扩增后获得高效价的重组杆状病毒,用SDS-PAGE、免疫荧光法和电镜检测目的蛋白的表达.结果 构建了以HPV16 L1为载体的M2e通用疫苗杆粒,通过转染sf9昆虫细胞得到初步M2e-HPV16 L1融合蛋白表达.结论 成功构建了HPV16 L1与甲型流感病毒M2e融合蛋白的病毒样颗粒,为流感通用疫苗的研制奠定了基础.     

疫苗接种的简要概述

正在美国,哈佛大学以及其他地方的研究人员都在极力寻找一种可以有效预防寨卡病毒的疫苗,这种蚊媒传播的疾病与罕见出生缺陷及格林·巴利综合症相关。与此同时,我们也有一些疫苗可以用于预防常见的疾病以及某些致命性疾病。然而,你是否需要考虑在今年接种流感疫苗、带状疱疹疫苗或肺炎疫苗呢?流感疫苗老年人建议每年接种一针流感疫苗,特别是那些患有心脏疾病的人。然而对于     

流行性感冒疫苗接种在心力衰竭中的研究进展

心力衰竭(心衰)患者预后较差,即使接受最佳药物治疗,心衰患者1年死亡率平均为33%,5年生存率不足50%。心衰患者往往合并多器官功能不全,免疫力较低,极易感染流行性感冒(流感)病毒。研究证明慢性心衰患者在流感季节的总体住院率明显升高,并且流感季节的慢性心衰患者总体死亡率也显著升高,提示流感可能是增加心衰患者再入院率和死亡率的重要因素。接种流感疫苗已被证实可降低急性心衰的发生率,降低慢性心衰患者的病死率并预防快速性心律失常的发生。因此,现综述流感疫苗接种在心衰中的研究进展,旨在为临床上改善心衰患者的预后提供理论依据。     

季节性流感防控措施

<正>近年来流感发病率急剧上升,即使是在中青年人群中也会引起危重症状甚至死亡。公共卫生部门、普通民众及临床医生应及时采取有效措施以降低其危害。建议6个月以上儿童及成人每年接种一次流感疫苗。流感疫苗的有效性取决于接种者的年龄及免疫反应状态,病毒株与疫苗株之间的匹配程度等。尽管在老年人和部分接种过疫苗的人群中还会     

Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases

Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses.     

In the Shadow of Hemagglutinin: A Growing Interest in Influenza Viral Neuraminidase and Its Role as a Vaccine Antigen

Despite the availability of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to have a significant, annual impact on the morbidity and mortality of human beings, highlighting the continued need for research in the field. Current vaccine strategies predominantly focus on raising a humoral response against hemagglutinin (HA)—the more abundant, immunodominant glycoprotein on the surface of the influenza virus. In fact, anti-HA antibodies are often neutralizing, and are used routinely to assess vaccine immunogenicity. Neuraminidase (NA), the other major glycoprotein on the surface of the influenza virus, has historically served as the target for antiviral drug therapy and is much less studied in the context of humoral immunity. Yet, the quest to discern the exact importance of NA-based protection is decades old. Also, while antibodies against the NA glycoprotein fail to prevent infection of the influenza virus, anti-NA immunity has been shown to lessen the severity of disease, decrease viral lung titers in animal models, and reduce viral shedding. Growing evidence is intimating the possible gains of including the NA antigen in vaccine design, such as expanded strain coverage and increased overall immunogenicity of the vaccine. After giving a tour of general influenza virology, this review aims to discuss the influenza A virus neuraminidase while focusing on both the historical and present literature on the use of NA as a possible vaccine antigen.     

Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge

Modified vaccinia virus Ankara (MVA), developed >30 years ago as a highly attenuated candidate smallpox vaccine, was recloned from a 1974 passage and evaluated for safety and immunogenicity. Replication of MVA is impaired in most mammalian cells, and we found that mice with severe combined immunodeficiency disease remained healthy when inoculated with MVA at 1,000 times the lethal dose of vaccinia virus derived from the licensed Dryvax vaccine seed. In BALB/c mice inoculated intramuscularly with MVA, virus-specific CD8+ T cells and antibodies to purified virions and membrane protein components of the intracellular and extracellular infectious forms of vaccinia virus were induced in a dose-dependent manner. After one or two inoculations of MVA, the T cell numbers and antibody titers equaled or exceeded those induced by percutaneous injection of Dryvax. Antibodies induced by MVA and Dryvax were neutralizing and inhibited virus spread in cultured cells. Furthermore, vaccinated mice were protected against lethal intranasal challenge with a pathogenic vaccinia virus. B cell-deficient mice unable to generate antibodies and beta2-microglobulin-deficient mice unable to express MHC class I molecules for a CD8+ T cell response were also protectively vaccinated by MVA. In contrast, mice with decreased CD4 or MHC class II expression and double-knockout mice deficient in MHC class I- and II-restricted activities were poorly protected or unprotected. This study confirmed the safety of MVA and demonstrated that the overlapping immune responses protected normal and partially immune-deficient animals, an encouraging result for this candidate attenuated smallpox vaccine.     

The pathogenesis and management of influenza virus infection in organ transplant recipients

Abstract: Infection with influenza viruses poses specific problems in adult and pediatric organ transplant recipients, including a higher rate of pulmonary and extra-pulmonary complications. Also, data suggest that influenza is associated with acute cellular rejection and chronic allograft dysfunction. The main strategy of influenza prevention has been influenza immunization in order to stimulate local and systemic antibodies. However, studies have shown that antibody response to inactivated influenza vaccine is decreased in all groups of organ transplant recipients. A live attenuated influenza virus vaccine is nearing approval in the United States. However, studies are needed in organ transplant recipients to determine whether the live attenuated influenza virus vaccine can enable these patients to mount a protective immune response and what degree of protection or amelioration of illness is provided by such vaccine. It is also important to verify the safety of this vaccine in organ transplant recipients because live virus may cause severe disease in these patients. Therefore, other modalities of prevention against influenza, such as chemoprophylaxis with antiviral drugs, should be considered in this patient population. The current review provides an overview of the incidence, clinical manifestations, and strategies for the prevention and management of influenza in organ transplant recipients.     

新甲型H1N1流感病毒与流感大流行防治研究进展

由于甲型流感病毒基因高度变异的特点,导致其对不同种属宿主亲和力、毒力、免疫原性、抗药性不断发生变化,全球新型流感大流行的风险时刻存在.因此,应加强流感特别是重症流感发病机制和有效干预措施研究,从疫苗研制、开发新型抗病毒药、加强综合治疗,特别是调节宿主免疫反应等多个方面着手,为应对可能爆发的流感大流行提供对策.     

Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1

Since 2003, the number of human cases of infections with highly pathogenic avian influenza viruses of the H5N1 subtype is still increasing, and, therefore, the development of safe and effective vaccines is considered a priority. However, the global production capacity of conventional vaccines is limited and insufficient for a worldwide vaccination campaign. In the present study, an alternative H5N1 vaccine candidate based on the replication-deficient modified vaccinia virus Ankara (MVA) was evaluated. C57BL/6J mice were immunized twice with MVA expressing the hemagglutinin (HA) gene from influenza virus A/Hongkong/156/97 (MVA-HA-HK/97) or A/Vietnam/1194/04 (MVA-HA-VN/04). Subsequently, recombinant MVA-induced protective immunity was assessed after challenge infection with 3 antigenically distinct strains of H5N1 influenza viruses: A/Hongkong/156/97, A/Vietnam/1194/04, and A/Indonesia/5/05. Our data suggest that recombinant MVA expressing the HA of influenza virus A/Vietnam/1194/04 is a promising alternative vaccine candidate that could be used for the induction of protective immunity against various H5N1 influenza strains.     

Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes

Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates protective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single α-helical portion of the HA2 protein. Our data further demonstrate that the specific design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.     

mRNA Vaccine Development for Emerging Animal and Zoonotic Diseases

In the prevention and treatment of infectious diseases, mRNA vaccines hold great promise because of their low risk of insertional mutagenesis, high potency, accelerated development cycles, and potential for low-cost manufacture. In past years, several mRNA vaccines have entered clinical trials and have shown promise for offering solutions to combat emerging and re-emerging infectious diseases such as rabies, Zika, and influenza. Recently, the successful application of mRNA vaccines against COVID-19 has further validated the platform and opened the floodgates to mRNA vaccine’s potential in infectious disease prevention, especially in the veterinary field. In this review, we describe our current understanding of the mRNA vaccines and the technologies used for mRNA vaccine development. We also provide an overview of mRNA vaccines developed for animal infectious diseases and discuss directions and challenges for the future applications of this promising vaccine platform in the veterinary field.     

Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus

The success of the World Health Organization smallpox eradication program three decades ago resulted in termination of routine vaccination and consequent decline in population immunity. Despite concerns regarding the reintroduction of smallpox, there is little enthusiasm for large-scale redeployment of licensed live vaccinia virus vaccines because of medical contraindications and anticipated serious side effects. Therefore, highly attenuated strains such as modified vaccinia virus Ankara (MVA) are under evaluation in humans and animal models. Previous studies showed that priming and boosting with MVA provided protection for >2 years in a monkeypox virus challenge model. If variola virus were used as a biological weapon, however, the ability of a vaccine to quickly induce immunity would be essential. Here, we demonstrate more rapid immune responses after a single vaccination with MVA compared to the licensed Dryvax vaccine. To determine the kinetics of protection of the two vaccines, macaques were challenged intravenously with monkeypox virus at 4, 6, 10, and 30 days after immunization. At 6 or more days after vaccination with MVA or Dryvax, the monkeys were clinically protected (except for 1 of 16 animals vaccinated with MVA), although viral loads and number of skin lesions were generally higher in the MVA vaccinated group. With only 4 days between immunization and intravenous challenge, however, MVA still protected whereas Dryvax failed. Protection correlated with the more rapid immune response to MVA compared to Dryvax, which may be related to the higher dose of MVA that can be tolerated safely.     

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.