Littérature scientifique sur le sujet « H5N1 influenza vaccine »
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Articles de revues sur le sujet "H5N1 influenza vaccine"
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Chua, Tze-Hoong, Connie Y. H. Leung, H. E. Fang, Chun-Kin Chow, Siu-Kit Ma, Sin-Fun Sia, Iris H. Y. Ng et al. « Evaluation of a Subunit H5 Vaccine and an Inactivated H5N2 Avian Influenza Marker Vaccine in Ducks Challenged with Vietnamese H5N1 Highly Pathogenic Avian Influenza Virus ». Influenza Research and Treatment 2010 (27 juin 2010) : 1–10. http://dx.doi.org/10.1155/2010/489213.
Texte intégralRésumé :
The protective efficacy of a subunit avian influenza virus H5 vaccine based on recombinant baculovirus expressed H5 haemagglutinin antigen and an inactivated H5N2 avian influenza vaccine combined with a marker antigen (tetanus toxoid) was compared with commercially available inactivated H5N2 avian influenza vaccine in young ducks. Antibody responses, morbidity, mortality, and virus shedding were evaluated after challenge with a Vietnamese clade 1 H5N1 HPAI virus [A/VN/1203/04 (H5N1)] that was known to cause a high mortality rate in ducks. All three vaccines, administered with water-in-oil adjuvant, provided significant protection and dramatically reduced the duration and titer of virus shedding in the vaccinated challenged ducks compared with unvaccinated controls. The H5 subunit vaccine was shown to provide equivalent protection to the other two vaccines despite the H5 antibody responses in subunit vaccinated ducks being significantly lower prior to challenge. Ducks vaccinated with the H5N2 marker vaccine consistently produced antitetanus toxoid antibody. The two novel vaccines have attributes that would enhance H5N1 avian influenza surveillance and control by vaccination in small scale and village poultry systems.
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Nuñez, Ivette A., Ying Huang et Ted M. Ross. « Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections ». Pathogens 10, no 11 (20 octobre 2021) : 1352. http://dx.doi.org/10.3390/pathogens10111352.
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H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses. Therefore, COBRA HA-based vaccines were updated in order to elicit protective antibodies against the current circulating clades of H5Nx viruses. Next-generation COBRA HA vaccines were designed to encompass the newly emerging viruses circulating in wild avian populations. HA amino acid sequences from avian and human H5 influenza viruses isolated between 2011–2017 were downloaded from the GISAID (Global Initiative on Sharing All Influenza Data). Mice were vaccinated with H5 COBRA rHA that elicited antibodies with hemagglutinin inhibition (HAI) activity against H5Nx viruses from five clades. The H5 COBRA rHA vaccine, termed IAN8, elicited protective immune responses against mice challenged with A/Sichuan/26621/2014 and A/Vietnam/1203/2004. This vaccine elicited antibodies with HAI activity against viruses from clades 2.2, 2.3.2.1, 2.3.4.2, 2.2.1 and 2.2.2. Lungs from vaccinated mice had decreased viral titers and the levels of cellular infiltration in mice vaccinated with IAN-8 rHA were similar to mice vaccinated with wild-type HA comparator vaccines or mock vaccinated controls. Overall, these next-generation H5 COBRA HA vaccines elicited protective antibodies against both historical H5Nx influenza viruses, as well as currently circulating clades of H5N1, H5N6, and H5N8 influenza viruses.
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Takada, Ayato, Noritaka Kuboki, Katsunori Okazaki, Ai Ninomiya, Hiroko Tanaka, Hiroichi Ozaki, Shigeyuki Itamura et al. « Avirulent Avian Influenza Virus as a Vaccine Strain against a Potential Human Pandemic ». Journal of Virology 73, no 10 (1 octobre 1999) : 8303–7. http://dx.doi.org/10.1128/jvi.73.10.8303-8307.1999.
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ABSTRACT In the influenza H5N1 virus incident in Hong Kong in 1997, viruses that are closely related to H5N1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possibility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surrogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an avirulent recombinant H5N1 virus generated by reverse genetics, have been explored. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inhibiting and virus-neutralizing antibodies, while intranasal vaccination without adjuvant induced both mucosal and systemic antibody responses that protected the mice from lethal H5N1 virus challenge. Surveillance of birds and animals, particularly aquatic birds, for viruses to provide vaccine strains, especially surrogate viruses, for a future pandemic is stressed.
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Banner, David, et Alyson Ann Kelvin. « The current state of H5N1 vaccines and the use of the ferret model for influenza therapeutic and prophylactic development ». Journal of Infection in Developing Countries 6, no 06 (15 mai 2012) : 465–69. http://dx.doi.org/10.3855/jidc.2666.
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Highly pathogenic avian influenza H5N1 is a threat to global public health as a natural pandemic causing agent but has recently been considered a bioterrorism concern. The evolving view of the H5N1 virus necessitates the re-evaluation of the current status of H5N1 therapeutics and prophylactics, in particular the preparation of viable H5N1 vaccination strategies as well as the use of ferrets in influenza research. Here the highly pathogenic H5N1 virus dilemma is discussed in context with the current H5N1 vaccine status and the use of the ferret model. Previously, the development of various H5N1 vaccine platforms have been attempted, many of them tested in the ferret model, including vector vaccines, adjuvant vaccines, DNA vaccines, and reverse engineered vaccines. Moreover, as ferrets are a superlative animal model for influenza investigation and vaccine testing, it is imperative that this model is recognized for its uses in prophylactic development and not only as an agent for creating transmissible influenza viruses. Elucidating the ferret immune response and creating ferret immune reagents remain important goals in conjunction with the development and manufacture of H5N1 vaccines. In summary, an efficacious H5N1 vaccine is urgently needed and the ferret model remains an appropriate model for its development.
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Ali, Ahmed, Marwa Safwat, Walid H. Kilany, Abdou Nagy, Awad A. Shehata, Mohamed A. Zain El-Abideen, Al-Hussien M. Dahshan et Abdel-Satar A. Arafa. « Combined H5ND inactivated vaccine protects chickens against challenge by different clades of highly pathogenic avian influenza viruses subtype H5 and virulent Newcastle disease virus ». Veterinary World 12, no 1 (janvier 2019) : 97–105. http://dx.doi.org/10.14202/vetworld.2019.97-105.
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Aim: The aim of the current study was to evaluate the efficacy of a trivalent-inactivated oil-emulsion vaccine against challenge by different clades highly pathogenic avian influenza (HPAI) viruses including HPAI-H5N8 and the virulent genotype VII Newcastle disease virus (NDV) (vNDV). Materials and Methods: The vaccine studied herein is composed of reassortant AI viruses rgA/Chicken/Egypt/ ME1010/2016 (clade 2.2.1.1), H5N1 rgA/Chicken/Egypt/RG-173CAL/2017 (clade 2.2.1.2), and "NDV" (LaSota NDV/ CK/Egypt/11478AF/11); all used at a concentration of 108 EID50/bird and mixed with Montanide-ISA70 oil adjuvant. Two-week-old specific pathogen free (SPF) chickens were immunized subcutaneously with 0.5 ml of the vaccine, and hemagglutination inhibition (HI) antibody titers were monitored weekly. The intranasal challenge was conducted 4 weeks post-vaccination (PV) using 106 EID50/0.1 ml of the different virulent HPAI-H5N1 viruses representing clades 2.2.1, 2.2.1.1, 2.2.1.2, 2.3.4.4b-H5N8, and the vNDV. Results: The vaccine induced HI antibody titers of >6log2 against both H5N1 and NDV viruses at 2 weeks PV. Clinical protection against all HPAI H5N1 viruses and vNDV was 100%, except for HPAI H5N1 clade-2.2.1 and HPAI H5N8 clade- 2.3.4.4b viruses that showed 93.3% protection. Challenged SPF chickens showed significant decreases in the virus shedding titers up to <3log10 compared to challenge control chickens. No virus shedding was detected 6 "days post-challenge" in all vaccinated challenged groups. Conclusion: Our results indicate that the trivalent H5ND vaccine provides significant clinical protection against different clades of the HPAI viruses including the newly emerging H5N8 HPAI virus. Availability of such potent multivalent oil-emulsion vaccine offers an effective tool against HPAI control in endemic countries and promises simpler vaccination programs.
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Lei, Han, Sha Jin, Erik Karlsson, Stacey Schultz-Cherry et Kaiming Ye. « Yeast Surface-Displayed H5N1 Avian Influenza Vaccines ». Journal of Immunology Research 2016 (2016) : 1–12. http://dx.doi.org/10.1155/2016/4131324.
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Highly pathogenic H5N1 avian influenza viruses pose a pandemic threat to human health. A rapid vaccine production against fast outbreak is desired. We report, herein, a paradigm-shift influenza vaccine technology by presenting H5N1 hemagglutinin (HA) to the surface of yeast. We demonstrated, for the first time, that the HA surface-presented yeast can be used as influenza vaccines to elicit both humoral and cell-mediated immunity in mice. The HI titer of antisera reached up to 128 in vaccinated mice. A high level of H5N1 HA-specific IgG1 and IgG2a antibody production was detected after boost immunization. Furthermore, we demonstrated that the yeast surface-displayed HA preserves its antigenic sites. It preferentially binds to both avian- and human-type receptors. In addition, the vaccine exhibited high cross-reactivity to both homologous and heterologous H5N1 viruses. A high level production of anti-HA antibodies was detected in the mice five months after vaccination. Finally, our animal experimental results indicated that the yeast vaccine offered complete protection of mice from lethal H5N1 virus challenge. No severe side effect of yeast vaccines was noted in animal studies. This new technology allows for rapid and large-scale production of influenza vaccines for prepandemic preparation.
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Kodihalli, Shantha, Hideo Goto, Darwyn L. Kobasa, Scott Krauss, Yoshihiro Kawaoka et Robert G. Webster. « DNA Vaccine Encoding Hemagglutinin Provides Protective Immunity against H5N1 Influenza Virus Infection in Mice ». Journal of Virology 73, no 3 (1 mars 1999) : 2094–98. http://dx.doi.org/10.1128/jvi.73.3.2094-2098.1999.
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ABSTRACT In Hong Kong in 1997, a highly lethal H5N1 avian influenza virus was apparently transmitted directly from chickens to humans with no intermediate mammalian host and caused 18 confirmed infections and six deaths. Strategies must be developed to deal with this virus if it should reappear, and prospective vaccines must be developed to anticipate a future pandemic. We have determined that unadapted H5N1 viruses are pathogenic in mice, which provides a well-defined mammalian system for immunological studies of lethal avian influenza virus infection. We report that a DNA vaccine encoding hemagglutinin from the index human influenza isolate A/HK/156/97 provides immunity against H5N1 infection of mice. This immunity was induced against both the homologous A/HK/156/97 (H5N1) virus, which has no glycosylation site at residue 154, and chicken isolate A/Ck/HK/258/97 (H5N1), which does have a glycosylation site at residue 154. The mouse model system should allow rapid evaluation of the vaccine’s protective efficacy in a mammalian host. In our previous study using an avian model, DNA encoding hemagglutinin conferred protection against challenge with antigenic variants that differed from the primary antigen by 11 to 13% in the HA1 region. However, in our current study we found that a DNA vaccine encoding the hemagglutinin from A/Ty/Ir/1/83 (H5N8), which differs from A/HK/156/97 (H5N1) by 12% in HA1, prevented death but not H5N1 infection in mice. Therefore, a DNA vaccine made with a heterologous H5 strain did not prevent infection by H5N1 avian influenza viruses in mice but was useful in preventing death.
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Sun, Weiyang, Zhenfei Wang, Yue Sun, Dongxu Li, Menghan Zhu, Menglin Zhao, Yutian Wang et al. « Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model ». Viruses 13, no 12 (3 décembre 2021) : 2420. http://dx.doi.org/10.3390/v13122420.
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H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.
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Skarlupka, Amanda L., Xiaojian Zhang, Uriel Blas-Machado, Spencer F. Sumner et Ted M. Ross. « Multi-Influenza HA Subtype Protection of Ferrets Vaccinated with an N1 COBRA-Based Neuraminidase ». Viruses 15, no 1 (9 janvier 2023) : 184. http://dx.doi.org/10.3390/v15010184.
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The influenza neuraminidase (NA) is a promising target for next-generation vaccines. Protection induced by vaccination with the computationally optimized broadly reactive NA antigen (N1-I COBRA NA) was characterized in both influenza serologically naive and pre-immune ferret models following H1N1 (A/California/07/2009, CA/09) or H5N1 (A/Vietnam/1203/2004, Viet/04) influenza challenges. The N1-I COBRA NA vaccine elicited antibodies with neutralizing ELLA activity against both seasonal and pandemic H1N1 influenza, as well as the H5N1 influenza virus. In both models, N1-I COBRA NA-vaccinated ferrets that were challenged with CA/09 virus had similar morbidity (weight loss and clinical symptoms) as ferrets vaccinated with the CA/09 HA control vaccine. There were significantly reduced viral titers compared to the mock-vaccinated control animals. Ferrets vaccinated with N1-I COBRA NA or Viet/04 NA vaccines were protected against the H5N1 virus infection with minimal clinical symptoms and negligible weight loss. In contrast, ferrets vaccinated with the CA/09 NA vaccine lost ~10% of their original body weight with 25% mortality. Vaccination with either HA or NA vaccines did not inhibit contact transmission of CA/09 virus to naïve cage mates. Overall, the N1-I COBRA vaccine elicited protective immune responses against both H1N1 and H5N1 infections and partially mitigated disease in contact-transmission receiving ferrets. These results indicate that the N1-I COBRA NA performed similarly to the CA/09 HA and NA positive controls. Therefore, the N1-I COBRA NA alone induces protection against viruses from both H5N1 and H1N1 subtypes, indicating its value as a vaccine component in broadly protective influenza vaccines.
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Thi Dung, Luu, Doan Huu Thien, Nguyen Thi Ly, Nguyen Thi Hong Dinh, Be Thi Tham, Nguyen Hoang Tung et Pham Van Hung. « RT-PCR test for specific indentification of influenzavirus (A/H5N1) in vaccine ». JOURNAL OF CONTROL VACCINES AND BIOLOGICALS, no 1 (31 décembre 2021) : 66–77. http://dx.doi.org/10.56086/jcvb.vi1.6.
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RT-PCR (Reverse transcription - Polymerase Chain Reaction) is applied to determine the presence of influenza virus A/ H5N1 in vaccine, and to develop an identity process for specific virus strain A/H5N1 in influenza vaccine A/H5N1. Selected samples included: Ivacflu-A/H5N1 vaccine (Institute of Vaccines and Biologicals), Vaxigrip vaccine (Sanofi Pasteur), Influenza virus strain A/ Vietnam/1194/2004(A/H5N1) (NIBSC) was used as positive control; vaccine Varivax (MSD) and DNA/RNA free water was used as negative controls. The results showed that virus strain A/H5N1 was identified as production of RT-PCR that were positive with amplified primer pairs of 2 specific gene sequences of HA whose length 428 and 249 bp. Before starting RT-PCR, it was necessary to eliminate aluminum and the components of RT-PCR reaction included: 5X QIAGEN OneStep RT-PCR Buffer(5µl); dNTP (1µl); forward and reverse primers (1,5 µl); Enzyme (1 µl), H2 O (10 µl), ARN template (5 µl) and thermal cycle of RT- PCR reaction was: 50oC (30 minutes); 95OC (15 minutes); 94OC (30 seconds); 55OC (30 seconds); 72OC (1 minute); 72OC (10 minutes), 45 cycles.
Thèses sur le sujet "H5N1 influenza vaccine"
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Leung, Ho-chuen, et 梁浩銓. « A study of H5N1-M2e-based universal influenza vaccine ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208568.
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The ectodomain of influenza matrix protein 2 (M2e) may be an ideal candidate in the development of influenza universal vaccine due to its highly conserved property among different subtypes/strains of influenza virus. M2e based vaccines have been extensively studied and potent cross-subtype/strain protections have been reported. However, more and more M2e mutants of influenza virus have been identified in recent years. It is still unclear whether M2e based vaccines are effective against these M2e mutants of influenza virus.
This study first evaluated cross-protection of an M2e tetrameric peptide vaccine based on H5N1 virus strain A/Vietnam/1194/04 (VN/1194-M2e) against lethal challenges of M2e mutants of H5N1 virus strain A/Hong Kong/156/97 (HK/156) and a novel H7N9 virus, because there are 3 or 5 amino acid differences between VN/1194-M2e and HK/156-M2e or VN/1194-M2e and H7N9-M2e. The results showed that the vaccination of VN/1194-M2e did not induce high level of cross-reactive antibodies against HK/156-M2e and just provided poor cross-protection against lethal challenge of HK/156 virus. In contrast, VN/1194-M2e vaccination induced high level of cross-reactive antibodies against H7N9-M2e. Consistently, the vaccination provided good cross-protection against lethal challenge of H7N9 virus. These results strongly suggested that some mutations in M2e, such as mutations at positions 10, 14 and 16 which found in HK/156 M2e, might affect the M2e vaccine efficacy, but some others, such as five mutations found in H7N9-M2e, might not be critical for the M2e immunogenicity.
This study then investigated the relationship between the M2e immunogenicity and amino acid mutations of the M2e. Beside VN/1194-M2e (P0), we synthesized additional 10 M2e mutant peptides which contain different single or multiple mutations. The 3D structures of these M2e peptides were predicted and analyzed. The prediction results showed that group 1 peptides (P0, P10, P14, P16, P18, P20 and P18-20) exhibited either irregular structures or loose hairpin structures which might associate with well exposure of antigenic epitope, whereas group 2 peptides (P10-14, P10-16, P14-16 and P10-14-16) formed tight hairpin structures in which antigenic epitope might bury inside their own secondary structure. Vaccination efficacies of these M2e peptides were evaluated in mice for antibody responses and cross-protection against lethal challenge of VN/1194 and HK/156 viruses. Our results showed that vaccinations of group 1 peptides induced high levels of cross-reactive antibodies against VN/1194-M2e and good cross-protection against lethal challenge of VN/1194 virus. However, vaccinations of group 2 peptides vaccinations induced significantly lower VN/1194-M2e antibody responses and poor cross-protection against lethal challenge of VN/119 virus. Furthermore, both group 1 and group 2 peptides could just induce low levels of cross-reactive antibodies against HK/156-M2e and poor protection against lethal challenge of HK/156 virus.
Although H5N1-M2e tetrameric peptide has been previously shown to protect mice from lethal challenges by different subtypes/strains of influenza virus, this study has shown that certain amino acid variations in M2e could weaken M2e immunogenicity but some others might not. The different secondary structures of M2es may probably associate with their immunogenicity. Our findings have provided valuable information for the development of M2e based universal vaccines.published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
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Buffone, Adam. « Characterization of Influenza H5N1 Nucleocapsid Protein for Potential Vaccine Design ». Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/20537.
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Avian influenza H5N1 causes occasional but serious infections in humans and efforts to produce vaccines against this strain continue. Current influenza vaccines are prophylactic and utilize the two major antigens, hemagglutinin and neuraminidase. NP is an attractive alternative antigen because it is highly conserved across all influenza strains, has been shown to increase the rate of viral clearance, and potential therapeutic vaccines would elicit cytotoxic T lymophcyte responses in an infected person. The NP antigen from H5N1 was characterized using a variety of physiochemical methods to gain insights into both the biological and physical properties of the antigen which are important from a regulatory viewpoint when considering therapeutic vaccines. Results obtained to date show that NP is relatively unstable and indicate that the conformation of the H5N1 NP antigen is highly dependent upon purification procedure, buffer conditions, pH and the presence or absence of RNA. These factors will need to be clearly defined and taken into consideration when manufacturing and regulating NP vaccine preparations.
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Wu, Wai-lan, et 胡慧蘭. « Antigenic characterisation of avian influenza H5N1 viruses in Asia : implications for vaccine strainselection ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508270.
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Wu, Wai-lan. « Antigenic characterisation of avian influenza H5N1 viruses in Asia : implications for vaccine strain selection / ». Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41508270.
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Koontz, Lauren M. « HPAI H5N1 : A GLOBAL PANDEMIC CONCERN, WITH IMPLICATIONS FOR PANDEMIC PREPERATION AND PUBLIC HEALTH POLICY ». Wright State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=wright1369475455.
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BORGOGNI, ERICA. « Profiling human cell-mediated immune response to pre-pandemic vaccination ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2009. http://hdl.handle.net/10281/7485.
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Annual influenza A infections affect 5-15% of the population, causing an estimate half million deaths per year worldwide, with the majority of the severe diseases in infants, elderly and immunocompromised individuals. Influenza viruses infect the epithelium of the upper and lower respiratory tracts, typically resulting in an abrupt onset of illness, that usually includes fever, myalgias, upper respiratory tract congestion and pharyngytis. These symptoms persist for approximately one week; pneumonia is a frequent manifestation of more severe infection, while myocarditis, encephalitis and other extra respiratory tract disease occur more ralely.
Influenza viruses belongs to Orthomixoviridae family, are enveloped negative single stranded RNA virus able to infect a wide range of avian and mammalian species. The genome of influenza A virus is composed of eight segments that encode for at least ten proteins. Influenza A viruses are subdivided further into subtypes based on their two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), and currently, 16 known types of HA and 9 known types of NA have been isolated from aquatic birds, the natural reservoir for all influenza viruses. Haemagglutinin (HA) and neuraminidase (NA) are the primary targets of influenza vaccines but also the viral surface glycoproteins that accumulate the highest number of mutations. Haemagglutinin, the most abundant surface glycoprotein, directs binding and viral entry into host cells whereas neuraminidase, the second most abundant surface glycoprotein, cleaves sialic acid and plays important roles in viral entry and release.
Influenza vaccination is the most effective method for preventing influenza virus infection and its potentially severe complications. Natural infection and vaccination elicit long lasting protective responses, nevertheless influenza vaccines are modified yearly due to the high propensity of the virus to mutate.
Minor mutations, antigenic drift, occur continuously due to the low fidelity of the RNA polymerase and support the need for yearly changes in vaccine strains. Major modifications in the virus, antigenic shift, arise from viral re-assortments, occur more rarely, but represent a major challenge for public health since they can give rise to novel viruses for which the human population has little or no immunity. The latter scenario creates the risk of a pandemic infection similar to the Spanish flu pandemic (1918-1920) resulting in more than 40 million deaths worldwide and to the Asian flu (1957) and the Hong Kong Flu (1968) resulting in 1-4 million deaths.
Occasionally, avian influenza A virus cross the species barrier into human and a pandemic may arise if such viruses have the ability to spread efficiently from human to human. In 1997, the increase in outbreaks of highly pathogenic avian influenza (HPAI) in poultry and the occasional transmission of these viruses to humans has caused great concern for the emergence of a new influenza A virus pandemics. Since then HPAI H5N1 viruses have continued to circulate in Asia and 400 human cases have been reported with a fatal outcome of 60%.
Protection from avian H5N1 influenza virus could be achieved by vaccines capable of eliciting sustained and broadly cross-reactive immune responses.
All clinical studies so far have shown the need for two doses of adjuvanted pre-pandemic flu vaccines to achieve potentially protective neutralizing antibody titers against avian H5N1 Vietnam. Two doses of avian influenza vaccines formulated with a strong adjuvant such as MF59 are required to induce potentially protective titers of neutralizing antibodies broadly reactive to drifted H5 strains. In addition all clinical studies have shown in influenza a limited efficacy of alum compared to oil in water emulsions, such as MF59, an adjuvant with excellent safety record licensed from more than a decade for seasonal flu vaccines in Europe.
Those studies also showed that years after priming even if antibodies become undetectable the immune-response can be efficiently boosted in subjects that received a successful priming regimen.
Such considerations support a prime boost strategy based on 1 or 2 immunizations for “pre pandemic vaccination” followed by a “booster dose” at the start of the pandemic outbreak. A drawback to this strategy is the lack of early markers capable of predicting the proportion of the population that develops a memory response after pre pandemic vaccination, information currently deduced only post hoc based on the response to the booster dose. To identify an early marker of effective pre pandemic priming we analyzed both the antibody and cell mediated responses in a prime boost clinical trial. We conducted a phase II study wherein healthy adults received 2 doses of a subunit H5N1 A/Vietnam/1194/2004 vaccine as “pre pandemic vaccination”, followed at 6 months by a 3rd booster dose. The vaccine was either plain (Non Adj 15) or adjuvanted with MF59 (MF59 H5N1), an oil/water proprietary adjuvant used in seasonal flu vaccines since 1997.
We found that one dose of MF59 H5N1 vaccine is sufficient to expand CD4+ T lymphocytes with a Th1-prone effector/memory phenotype; whereas 2 doses are required to expand the pool of H5N1 memory B cells and to elicit high titers of neutralizing antibodies.
Strikingly, a 3 fold increase in total H5 specific CD4+ T cells after the 1st dose predicts the rise of MN antibodies to titers ≥80 after booster immunization and their persistence at 6 months with 75% and 85% accuracy, respectively. We suggest that, if confirmed on a larger number of subjects, CD4+ T cell priming can be used as early measure of vaccine efficacy and can help screen different pre-pandemic vaccine formulations for their ability to induce immune-memory.
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Bouscambert-Duchamp, Maude. « Étude du réassortiment génétique des virus influenza d’origines et de sous-types différents ». Thesis, Lyon 1, 2010. http://www.theses.fr/2010LYO10084/document.
Texte intégralRésumé :
Dans le contexte de la menace pandémique liée au virus influenza A(H5N1), un projet «GRIPPE AVIAIRE ET GRIPPE PANDÉMIQUE » a émergé au sein de LyonBioPôle avec comme objectif le développement d’outils de caractérisation des virus influenza pour la production de vaccins. Pour étudier le réassortiment génétique entre virus influenza, nous avons développé 3 systèmes de génétique inverse : virus humain A(H3N2) et aviaires A(H5N2) et A(H5N1) et produit des virus réassortants de composition déterminée. Leurs capacités réplicatives ont été évaluées par cinétiques de croissance virale sur MDCK avec quantification de la production virale par qRT-PCR temps réel. L’émergence du virus influenza A(H1N1)2009 pose deux questions sur l’acquisition par réassortiment génétique, d’une résistance à l’oseltamivir d’une part ou de facteurs de virulence d’autre part. Nous avons donc développé un protocole de co-infection virale de cellules MDCK pour étudier les constellations de gènes des réassortants entre différents virus: A(H1N1)2009-A(H1N1) H275Y et A(H1N1)2009-A(H5N1). Nous montrons par deux approches différentes, génétique inverse et co-infections virales, que le réassortiment génétique entre souches aviaires et humaines et surtout aviaires et porcines est possible, en privilégiant certaines constellations. Nous rapportons que le virus pandémique peut acquérir la NA H275Y des virus A(H1N1) Brisbane-like résistants à l’oseltamivir sans que ses capacités de réplication ne soient altérées. De même nous montrons que son réassortiment avec un virus hautement pathogène A(H5N1) est possible. Ces observations renforcent la nécessité de promouvoir la vaccination afin de limiter les risques de co-infection virale chez un même individuIn the context of A(H5N1) pandemics threat, an « avian flu and flu pandemics » project was proposed by LyonBioPole to develop influenza viruses characterization tools for vaccine production. To study genetic reassortment between influenza viruses, 3 reverse genetic systems of A(H3N2) human virus and A(H5N2) and A(H5N1) avian viruses were developed and reassortant viruses were produced. Their replicative capacities were evaluated using growth kinetics on MDCK cells with viral production quantification by real-time qRT-PCR. The A(H1N1)2009 emergence raises two questions about the acquisition by genetic reassortment of oseltamivir resistance and/or pathogenicity determinants. A co-infection protocol on MDCK cells was developed to study gene constellations of reassortant viruses like A(H1N1)2009-A(H1N1) H275Y and A(H1N1)2009-A(H5N1). We report here that genetic reassortment is possible between avian, human and swine strains using reverse genetic and viral co-infection and that some specific constellations emerged. We also report, that pandemic A(H1N1)2009 can acquire the H275Y mutated NA from seasonal oseltamivir resistant A(H1N1) viruses without any modifications on replicative capacities. This genetic reassortment is also possible with A(H5N1) viruses. These observations strenght the importance of vaccination against all these influenza strains to reduce the risk of one-individual viral co-infection
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Chen, Ming-Wei, et 陳名偉. « Influenza H5N1 Hemagglutinin-Based DNA Vaccine Research ». Thesis, 2010. http://ndltd.ncl.edu.tw/handle/53909607269653083845.
Texte intégralRésumé :
博士國立陽明大學
生化暨分子生物研究所
99
H5N1 influenza viruses have spread extensively among wild birds and domestic poultry. Cross-species transmission of these viruses to humans has been documented in over 502 cases, with a mortality rate of ~60%. There is a great concern that a H5N1 virus would acquire the ability to spread efficiently between humans, thereby becoming a pandemic threat. A H5N1 influenza vaccine, therefore, become an integral part of any pandemic preparedness plan. However, traditional methods of making influenza vaccines have yet to produce the candidates that could induce potent neutralizing antibodies against divergent strains of H5N1 influenza viruses. To address this need, we generated a consensus H5N1 hemagglutinin (HA) sequence based on data available in early 2006. This sequence was then optimized for protein expression before being inserted into a DNA plasmid (pCHA5). Immunizing mice with pCHA5 by electroporation (EP), elicited antibodies that neutralized a panel of virions that have been pseudotyped with the HA from various H5N1 viruses (in-vitro). Moreover, immunization with pCHA5 in mice conferred complete (clades 1 and 2.2) or significant (clade 2.1) protection from H5N1 virus challenges (in-vivo). The consensus HA DNA vaccine combined with EP delivery gave a great protection against H5N1 influenza virus in mouse model. This is the first time that consensus DNA vaccine via IM/EP injection that can elicit the broadest cross-neutralization and cross-protection activity to against all the divergent influenza H5N1 viruses in different clades. Furthermore, the establishment of correlation of in-vitro neutralization and in-vivo challenge studies also enabled us to conduct a comprehensive analysis on serotyping characteristics of the HA from representative H5N1 viruses. The results not only confirmed that cross-clade immunity of consensus DNA vaccine was indeed contributed by the DNA sequence, but also established a platform to efficiently evaluate the cross-protection profiles of a given HA sequence. With this platform, the correlation between HA genotype and serotype can be successfully investigated for the vaccine strain candidate to be decided precisely. The vaccine antigen designed based on consensus strategy showed the superior cross-neutralization activity than WHO-suggested vaccine strains. Particularly for the second-generation consensus HA sequence, pCHA5II, can induce antiserum with better cross-neutralization activity than pCHA5 does, especially to the most recent circulating clade 2.3 viruses. It is noteworthy that, our cross-neutralization results are highly correlated to in-vivo challenge results. Based on our research here, we conclude that HA DNA vaccine which can induce cross-immunity (e.g., pCHA5/pCHA5II), combined with EP delivery is a promising strategy to induce antibodies with better cross-reactivities against divergent H5N1 influenza viruses. Thus, we conclude that this consensus HA-based vaccine could induce broad protection against divergent H5N1 influenza viruses. This is the first time by using HA DNA vaccine-induced antiserum against a set of H5N1 pseudotyped viruses to establish the correlation between the H5N1 HA antigenicity within genotype and immunogenicity within serotype. The highly reliable results could be the one of references for vaccine strain decision. Moreover, we were interested in examining the amino acid mutation or glycosylation modification in the HA globular region of pCHA5-immune escaping virus strains. Based on genetic alignment revealed that most of the amino acid differences between CHA5 and those insusceptible strains were at the receptor binding domain with the most significant one at the 157th residue. When we immunized mice with HA harboring 157P, the elicited antibodies showed increased neutralizing activity against the clade 2.3 viruses. Likewise, the viruses pseudotyped with hemagglutinin containing 157S become more susceptible to neutralization. The correlation between escape capability from CHA5-vaccinated immunity and sialosides binding activities were confirmed by sugar binding analysis of HA containing 157P or 157S. It was concluded that the S157P amino acid substitution of hemagglutinin can alter antigenicity, immunogenicity, and binding avidity of H5N1 viruses. Overall, in this comprehensive study, we established a promising universal vaccine against H5N1 influenza virus and provided a system for vaccine strain decision and development. We also revealed the possible mechanism for influenza virus evading from vaccinated-immunity which combined with glycan microarray results that could be the highly sensitive surveillance system for flu pandemic.
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Patel, Ami. « Comparative evaluation of human and porcine adenovirus vectors for vaccine application agianst avian influenza (H5N1) ». 2011. http://hdl.handle.net/1993/4529.
Texte intégralRésumé :
First in 1997, and later re-emerging in 2003, highly pathogenic avian influenza A virus, subtype H5N1, has spread from wild bird reservoirs to domestic bird flocks. As a result, cross-transmission has been confirmed in people living or working in close contact with infected birds. H5N1 virus infection is associated with a high mortality rate (>60%) in humans and the rapid evolution of the virus suggests that it could potentially develop into a new, and possibly severe, pandemic influenza virus. To-date, conventional inactivated and live-attenuated vaccine strategies offers the best protection against influenza virus infection; however, poor immunogenicity and weaker efficacy have been observed against H5N1 viruses. It was hypothesized that experimental adenovirus-based vaccines based on human adenovirus serotype 5 (AdHu5) or porcine adenovirus serotype 3 (PAV3) can offer protection against a broad range of avian influenza, subtype H5N1, viruses. Ad vaccine vectors are highly immunogenic and have demonstrated protective efficacy against several disease models. However, natural immunity against AdHu5 can interfere with vector efficacy. The nonhuman PAV3 was not neutralized by pooled human serum from 10,000-60,000 individuals and offers a promising alternative to AdHu5-based vectors. Systematic antigen screening using DNA vaccines identified the hemagglutinin (HA) glycoprotein as the most immunogenic H5N1 antigen. HA was then inserted directly into PAV3 or AdHu5. Comparable immune responses were observed between both vectors but, interestingly, the PAV3-based vaccine generated stronger T-cell responses and better rapid protection 8 days following immunization. Additionally, better long-term protection 1 year following vaccination was observed with the PAV3-HA vaccine. The co-administration of multiple H5N1 antigens was also screened to improve protection against divergent H5N1 challenge. Combinations of DNA vaccines expressing (HA+NA) and (HA+NP) offered the best promise for enhancing protection against homologous and heterologous H5N1 challenges, respectively. However, addition of three or more antigens reduced overall protection possibly by antigen dilution, competition, or interference. Co-administration of PAV3 or AdHu5 vectors expressing both the HA and NP antigens reduced protection against homologous and heterologous H5N1 virus challenges. For all combination vaccines, T-cell responses were strong against HA but significantly decreased against additional antigens in each combination vaccine. Overall, the experimental porcine-based Ad-based vaccine offered better protection than the H5N1 conventional vaccine against a broad range of different H5N1 viruses. Understanding of the relationship between immune parameters and protection will be critical in future improvement of adenovirus-based and other vaccines against avian influenza H5N1.
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Isoda, Norikazu. « Studies on the pathogenicity and vaccine development of H5N1 highly pathogenic avian influenza virus strains ». Doctoral thesis, 2008. http://hdl.handle.net/2115/39062.
Texte intégralRésumé :
1997 年香港で発生して以来、H5N1 ウイルスによる高病原性鳥インフルエンザの発生が続いている。筆者は2004 年、日本で発生した高病原性鳥インフルエンザの病原ウイルスであるA/chicken/Yamaguchi/7/2004 (H5N1) (山口株) および、2005 年モンゴルのErkhel 湖で発見されたオオハクチョウの斃死体から分離された高病原性鳥インフルエンザウイルス、A/whooper swan/Mongolia/3/2005(H5N1) (モンゴル株) の鳥類および哺乳動物に対する病原性を実験室内で確認した。山口株は調べた4 つの鳥類に対して高い病原性を示し、全身感染を起こすことが分かった。しかし、マウスに対する病原性は低く、ミニブタには感染しなかった。モンゴル株は、山口株に対する感受性が低かった幼ガモおよびマウスに高い病原性を示し、さらにミニブタには感染することが確認された。これらの結果から、山口株は鳥類に対して非常に高い病原性を示すが、哺乳類には病原性が低いものと考えられる。またモンゴル株は山口株よりも多くの種類の動物に対して病原性を示し、ミニブタに感染することから、公衆衛生上非常に重要であることが示唆された。次にＨ5 ウイルスによる高病原性鳥インフルエンザに対して有効なワクチンの開発およびその評価を行った。高病原性鳥インフルエンザの防疫の基本は摘発淘汰であるが、防圧困難な非常時に備え、高力価のワクチンを開発および備蓄することが必要である。そこで筆者はH5N2 およびH7N1 亜型の2 株の非病原性ウイルスからH5N1 亜型の遺伝子再集合ウイルスを実験室内で作出し、それをワクチン株とした。ワクチン株を鶏胚尿膜腔内に接種して得た尿液のウイルスを不活化し、256.512HA/0.1ml 相当の油中水型ワクチンを試製した。ワクチン0.5ml をニワトリ4 週齢のニワトリの下脚部筋肉内に1 回注射し、免疫3 週後にワクチン株と抗原性が類似する山口株または抗原性が異なるモンゴル株で攻撃したところ、いずれの場合もニワトリは臨床症状を示すことなく14 日間耐過した。さらに、免疫後の日数が異なるニワトリに、HPAI ウイルス株にて攻撃したところ、ワクチン接種後6 日以内のニワトリは攻撃ウイルスにより全て死亡したが、ワクチン接種8 日目のニワトリはHI 抗体が検出されないにも関わらず、HPAI ウイルスの攻撃に対して耐過した。これらの結果から、本ワクチンはアジアで近年流行している高病原性鳥インフルエンザの病原ウイルスに有効であり、発症防御効果も接種8 日目から確認されたことから、緊急用ワクチンとして有用であることが判った。Hokkaido University (北海道大学)
博士
獣医学
Livres sur le sujet "H5N1 influenza vaccine"
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National Institute of Allergy and Infectious Diseases (U.S.) et National Institutes of Health (U.S.), dir. Results from a clinical trial demonstrate that high doses of an experimental H5N1 avian influenza vaccine can induce immune responses in healthy adults. [Washington, D.C.?] : National Institutes of Health, 2006.
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Wong, Jonathan P. Recent developments on the avian influenza (H5N1) crisis, 2006. Trivandrum, Kerala, India : Transworld Research Network, 2006.
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Siegel, Marc. Bird flu : Everything you need to know about the next pandemic. Hoboken, N.J : Wiley, 2006.
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News, PM Medical Health. 2006 Great Influenza Pandemic Guide : Federal Pandemic Influenza Plan, H5N1 Bird Flu, Public Health Guidelines, Drugs, Vaccines, CDC Data. Progressive Management, 2005.
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Siegel, Marc. Bird Flu : Everything You Need to Know About the Next Pandemic. Wiley, 2006.
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US GOVERNMENT. 2006 Essential Guide to Influenza : Medical Data about Influenza, Vaccines, Tamiflu and other Drugs, Avian Flu and the H5N1 Virus, Government Documents and Data (Ring-bound). Progressive Management, 2005.
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News, PM Medical Health. 21st Century Collection Centers for Disease Control Emerging Infectious Diseases (EID) Guide to Bird Flu and Pandemic Influenza : H5N1 Avian Flu, Drugs, Tamiflu, Vaccines. Progressive Management, 2005.
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US GOVERNMENT. 2006 Complete Guide to Bird Flu and Killer Influenza Pandemics Drugs, Tamiflu, Avian Flu Pandemic Preparations, Vaccines, Medical Guidelines and Research, H5N1 Virus (CD-ROM). Progressive Management, 2005.
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GOVERNMENT, US. 2006 If the Bird Flu Pandemic Strikes : Crucial Survival and Medical Data about Influenza, Vaccines, Tamiflu and other Drugs - Avian Flu and the H5N1 Virus (CD-ROM). Progressive Management, 2005.
Trouver le texte intégralChapitres de livres sur le sujet "H5N1 influenza vaccine"
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Fidler, David P. « Negotiating Equitable Access to Influenza Vaccines : Global Health Diplomacy and the Controversies Surrounding Avian Influenza H5N1 and Pandemic Influenza H1N1 ». Dans Negotiating and Navigating Global Health, 161–72. WORLD SCIENTIFIC, 2011. http://dx.doi.org/10.1142/9789814368049_0008.
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Vaughan, Sarah E., Robert C. Layton, Andrew P. Gigliotti, Zemmie E. Pollock, Jennifer R. Plourde, Zachary S. Karim, John A. Pyles et Kevin S. Harrod. « H5N1 Influenza Vaccine Does Not Produce Protective Immunity In BALB/c Mice ». Dans American Thoracic Society 2011 International Conference, May 13-18, 2011 • Denver Colorado. American Thoracic Society, 2011. http://dx.doi.org/10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a1814.
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