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1.
Conventional influenza vaccines are based on predicting the circulating viruses year by year, conferring limited effectiveness since the antigenicity of vaccine strains does not always match the circulating viruses. This necessitates development of universal influenza vaccines that provide broader and lasting protection against pan-influenza viruses. The discovery of the highly conserved immunogens(epitopes) of influenza viruses provides attractive targets for universal vaccine design. Here we review the current understanding with broadly protective immunogens(epitopes) and discuss several important considerations to achieve the goal of universal influenza vaccines. 相似文献
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《Microbes and infection / Institut Pasteur》2015,17(2):123-134
The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines. 相似文献
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The increasing number of reports of direct transmission of avian influenza viruses to humans underscores the need for control strategies to prevent an influenza pandemic. Vaccination is the key strategy to prevent severe illness and death from pandemic influenza. Despite long-term experience with vaccines against human influenza viruses, researchers face several additional challenges in developing human vaccines against avian influenza viruses. In this Review, we discuss the features of avian influenza viruses, the gaps in our understanding of infections caused by these viruses in humans and of the immune response to them that distinguishes them from human influenza viruses, and the current status of vaccine development. 相似文献
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流感严重地影响人们的身体健康和工作生活,给社会带来巨大经济损失。疫苗接种是预防流感的有效措施之一,市场上的流感疫苗包括流感灭活疫苗、减毒活疫苗和亚单位疫苗等。这些流感疫苗只能预防相同亚型流感病毒的感染,无法预防不同亚型流感病毒引起的季节性流感和流感大流行,因此迫切需要研发广谱的能预防不同亚型的甲型流感病毒感染的通用疫苗。在此简要介绍甲型流感病毒M2e通用疫苗的研究进展。 相似文献
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Influenza virus-specific cytotoxic T lymphocytes: a correlate of protection and a basis for vaccine development 总被引:2,自引:0,他引:2
Since influenza A viruses of the H5N1 subtype continue to circulate in wild and domestic birds and cause an ever increasing number of human cases, it is feared that H5N1 viruses may cause the next influenza pandemic. Therefore, there is considerable interest in the development of vaccines that confer protection against infections with these viruses or ideally, protection against influenza viruses of different subtypes. For the development of broad-protective vaccines the induction of virus-specific cytotoxic T lymphocytes (CTL) may be an important target, since it has been demonstrated that CTL contribute to protective immunity and are largely directed to epitopes shared by influenza viruses of various subtypes. In the present paper, the possibility to develop (cross-reactive) CTL-inducing vaccines is discussed. 相似文献
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Mariana Baz Myeisha Paskel Yumiko Matsuoka James Zengel Xing Cheng Hong Jin Kanta Subbarao 《Journal of virology》2013,87(12):6901-6910
Since it is difficult to predict which influenza virus subtype will cause an influenza pandemic, it is important to prepare influenza virus vaccines against different subtypes and evaluate the safety and immunogenicity of candidate vaccines in preclinical and clinical studies prior to a pandemic. In addition to infecting humans, H3 influenza viruses commonly infect pigs, horses, and avian species. We selected 11 swine, equine, and avian H3 influenza viruses and evaluated their kinetics of replication and ability to induce a broadly cross-reactive antibody response in mice and ferrets. The swine and equine viruses replicated well in the upper respiratory tract of mice. With the exception of one avian virus that replicated poorly in the lower respiratory tract, all of the viruses replicated in mouse lungs. In ferrets, all of the viruses replicated well in the upper respiratory tract, but the equine viruses replicated poorly in the lungs. Extrapulmonary spread was not observed in either mice or ferrets. No single virus elicited antibodies that cross-reacted with viruses from all three animal sources. Avian and equine H3 viruses elicited broadly cross-reactive antibodies against heterologous viruses isolated from the same or other species, but the swine viruses did not. We selected an equine and an avian H3 influenza virus for further development as vaccines. 相似文献
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Maeda Y Hatta M Takada A Watanabe T Goto H Neumann G Kawaoka Y 《Journal of virology》2005,79(11):6674-6679
Influenza and human parainfluenza virus infections are of both medical and economical importance. Currently, inactivated vaccines provide suboptimal protection against influenza, and vaccines for human parainfluenza virus infection are not available, underscoring the need for new vaccines against these respiratory diseases. Furthermore, to reduce the burden of vaccination, the development of multivalent vaccines is highly desirable. Thus, to devise a single vaccine that would elicit immune responses against both influenza and parainfluenza viruses, we used reverse genetics to generate an influenza A virus that possesses the coding region for the hemagglutinin/neuraminidase ectodomain of parainfluenza virus instead of the influenza virus neuraminidase. The recombinant virus grew efficiently in eggs but was attenuated in mice. When intranasally immunized with the recombinant vaccine, all mice developed antibodies against both influenza and parainfluenza viruses and survived an otherwise lethal challenge with either of these viruses. This live bivalent vaccine has obvious advantages over combination vaccines, and its method of generation could, in principle, be applied in the development of a "cocktail" vaccine with efficacy against several different infectious diseases. 相似文献
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L'vov DK 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2006,(3):96-100
Own results and literature data under the analysis of variability of a influenza virus A and population interactions in biological system: influenza virus A--wild and domestic animals--human are presented. Opportunities of virus reassortants appearance between viruses of animals and viruses of human and spreading the new pandemic variants are proved, in particular, at simultaneous infection of pigs with virus H5 and viruses of human influenza H1 and H3, circulating worldwide. Blocks of preparation to a flu pandemic, including on vaccine prophylactic are stated. It is discussed, what vaccines it is necessary to prepare. Inadmissibility the use of alive influenza vaccines is emphasized. 相似文献
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Pathogenicity and vaccine efficacy of different clades of Asian H5N1 avian influenza A viruses in domestic ducks 总被引:1,自引:0,他引:1
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Kim JK Seiler P Forrest HL Khalenkov AM Franks J Kumar M Karesh WB Gilbert M Sodnomdarjaa R Douangngeun B Govorkova EA Webster RG 《Journal of virology》2008,82(22):11374-11382
Waterfowl represent the natural reservoir of all subtypes of influenza A viruses, including H5N1. Ducks are especially considered major contributors to the spread of H5N1 influenza A viruses because they exhibit diversity in morbidity and mortality. Therefore, as a preventive strategy against endemic as well as pandemic influenza, it is important to reduce the spread of H5N1 influenza A viruses in duck populations. Here, we describe the pathogenicity of dominant clades (clades 1 and 2) of H5N1 influenza A viruses circulating in birds in Asia. Four representatives of dominant clades of the viruses cause symptomatic infection but lead to different profiles of lethality in domestic ducks. We also demonstrate the efficacy, cross-protectiveness, and immunogenicity of three different inactivated oil emulsion whole-virus H5 influenza vaccines (derived by implementing reverse genetics) to the viruses in domestic ducks. A single dose of the vaccines containing 1 μg of hemagglutinin protein provides complete protection against a lethal A/Duck/Laos/25/06 (H5N1) influenza virus challenge, with no evidence of morbidity, mortality, or shedding of the challenge virus. Moreover, two of the three vaccines achieved complete cross-clade or cross-subclade protection against the heterologous avian influenza virus challenge. Interestingly, the vaccines induce low or undetectable titers of hemagglutination inhibition (HI), cross-HI, and/or virus neutralization antibodies. The mechanism of complete protection in the absence of detectable antibody responses remains an open question. 相似文献
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Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns regarding their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity better than inactivated vaccines while also requiring a smaller dose to achieve a protective immune response. To address the need for a reassortment-incompetent live influenza A virus vaccine, we have designed a chimeric virus that takes advantage of the fact that influenza A and B viruses do not reassort. Our novel vaccine prototype uses an attenuated influenza B virus that has been manipulated to express the ectodomain of the influenza A hemagglutinin protein, the major target for eliciting neutralizing antibodies. The hemagglutinin RNA segment is modified such that it contains influenza B packaging signals, and therefore it cannot be incorporated into a wild-type influenza A virus. We have applied our strategy to different influenza A virus subtypes and generated chimeric B/PR8 HA (H1), HK68 (H3), and VN (H5) viruses. All recombinant viruses were attenuated both in vitro and in vivo, and immunization with these recombinant viruses protected mice against lethal influenza A virus infection. Overall, our data indicate that the chimeric live-attenuated influenza B viruses expressing the modified influenza A hemagglutinin are effective LAIVs. 相似文献
11.
Teresa Lambe 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1153-1160
Influenza represents a substantial global healthcare burden, with annual epidemics resulting in 3–5 million cases of severe illness with a significant associated mortality. In addition, the risk of a virulent and lethal influenza pandemic has generated widespread and warranted concern. Currently licensed influenza vaccines are limited in their ability to induce efficacious and long-lasting herd immunity. In addition, and as evidenced by the H1N1 pandemic in 2009, there can be a significant delay between the emergence of a pandemic influenza and an effective, antibody-inducing vaccine. There is, therefore, a continued need for new, efficacious vaccines conferring cross-clade protection—obviating the need for biannual reformulation of seasonal influenza vaccines. Development of such a vaccine would yield enormous health benefits to society and also greatly reduce the associated global healthcare burden. There are a number of alternative influenza vaccine technologies being assessed both preclinically and clinically. In this review we discuss viral vectored vaccines, either recombinant live-attenuated or replication-deficient viruses, which are current lead candidates for inducing efficacious and long-lasting immunity toward influenza viruses. These alternate influenza vaccines offer real promise to deliver viable alternatives to currently deployed vaccines and more importantly may confer long-lasting and universal protection against influenza viral infection. 相似文献
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《Microbes and infection / Institut Pasteur》2017,19(12):567-569
China is a major source of avian influenza viruses (AIVs) with bird-to-human transmissibility. Thus, understanding these viruses and treating infections at their source should decrease spread of AIVs to other countries in the world. This special issue focuses on the molecular epidemiology and pathogenesis of influenza viruses, and provides results on current efforts to develop vaccines against AIVs. 相似文献
14.
Carina Helmeke Lutz Gr?fe Hanns-Martin Irmscher Constanze Gottschalk Ioannis Karagiannis Hanna Oppermann 《PloS one》2015,10(4)
A live attenuated influenza vaccine has been available in Germany since the influenza season 2012/13, which is approved for children aged 2-17 years. Using data from our laboratory-based surveillance system, we described the circulation of influenza and non-influenza respiratory viruses during the influenza season 2012/13 in Saxony-Anhalt. We estimated the effectiveness of live and inactivated trivalent influenza vaccines in preventing laboratory-confirmed cases among children and adolescents. From week 40/2012 to 19/2013, sentinel paediatricians systematically swabbed acute respiratory illness patients for testing of influenza and 5 non-influenza viruses by PCR. We compared influenza cases and influenza-negative controls. Among children aged 2-17 years, we calculated overall and vaccine type-specific effectiveness against laboratory-confirmed influenza, stratified by age group (2-6; 7-17 years). We used multivariable logistic regression to adjust estimates for age group, sex and month of illness. Out of 1,307 specimens, 647 (35%) were positive for influenza viruses and 189 (15%) for at least one of the tested non-influenza viruses. For vaccine effectiveness estimation, we included 834 patients (mean age 7.3 years, 53% males) in our analysis. Of 347 (42%) influenza-positive specimens, 61 (18%) were positive for A(H1N1)pdm09, 112 (32%) for A(H3N2) and 174 (50%) for influenza B virus. The adjusted overall vaccine effectiveness including both age groups was 38% (95% CI: 0.8-61%). The adjusted effectiveness for inactivated vaccines was 37% (95% CI: -35-70%) and for live vaccines 84% (95% CI: 45-95%). Effectiveness for the live vaccine was higher in 2-6 year-old children (90%, 95% CI: 20-99%) than in children aged 7-17 years (74%, 95% CI: -32-95%). Our study of the strong influenza season in 2012/13 suggests a high preventive effect of live attenuated influenza vaccine especially among young children, which could not be reached by inactivated vaccines. We recommend the use of live attenuated influenza vaccines in children unless there are contraindications. 相似文献
15.
The evolution of human influenza viruses. 总被引:11,自引:0,他引:11
A J Hay V Gregory A R Douglas Y P Lin 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2001,356(1416):1861-1870
The evolution of influenza viruses results in (i) recurrent annual epidemics of disease that are caused by progressive antigenic drift of influenza A and B viruses due to the mutability of the RNA genome and (ii) infrequent but severe pandemics caused by the emergence of novel influenza A subtypes to which the population has little immunity. The latter characteristic is a consequence of the wide antigenic diversity and peculiar host range of influenza A viruses and the ability of their segmented RNA genomes to undergo frequent genetic reassortment (recombination) during mixed infections. Contrasting features of the evolution of recently circulating influenza AH1N1, AH3N2 and B viruses include the rapid drift of AH3N2 viruses as a single lineage, the slow replacement of successive antigenic variants of AH1N1 viruses and the co-circulation over some 25 years of antigenically and genetically distinct lineages of influenza B viruses. Constant monitoring of changes in the circulating viruses is important for maintaining the efficacy of influenza vaccines in combating disease. 相似文献
16.
M P Zykov A V Sosunov 《Journal of hygiene, epidemiology, microbiology, and immunology》1987,31(4):453-459
Reactogenicity, immunogenicity and viability of the vaccine virus were studied during vaccination of adults with live allantoic influenza vaccines of the types A (H1N1), A (H3N2) and B in different seasons of the year. Seasonal oscillations of reactogenicity of the vaccines (minimum in summer, maximum in winter) were demonstrated. A decrease in the re-isolation rate of vaccine viruses and in their content in the secretions of the upper respiratory passages was observed in summer. Seasonal oscillations of immunogenicity of the commercial live allantoic influenza vaccine with a marked reduction in its activity in summer were established. The administration of moderately attenuated influenza vaccine viruses in summer results in the production of antibodies up to the level observed in other seasons of the year. Theoretical problems and practical aspects of seasonal oscillations of vaccination activity of live influenza vaccines were studied in connection with the necessity of investigation new vaccine strains in varying seasons of the year. 相似文献
17.
Ze LIU Wei-dong LI Ming-bo SUN Lei MA Zi-quan GUO Shu-de JIANG Guo-yang LIAO Jing-si YANG Chang-gui LI 《Virologica Sinica》2010,(1)
Due to the insufficient supply of embryonated chicken eggs,the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus.The Vero cell is one of the ideal options since it was used for producing many kinds of human vaccines.However,most of the influenza viruses can not grow well in Vero cells.To develop a new influenza vaccine with Vero cells as a substrate,the virus needs to adapt to th... 相似文献
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J Vergara-Alert JM Argilaguet N Busquets M Ballester GE Martín-Valls R Rivas S López-Soria D Solanes N Majó J Segalés V Veljkovic F Rodríguez A Darji 《PloS one》2012,7(7):e40524
Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines à la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM). This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses than conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations. 相似文献