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Influenza A H5N1 (Avian Flu) Hemagglutinin, HA ELISA Kit

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[#DEIA250] Influenza A H5N1 (Avian Flu) Hemagglutinin, HA ELISA Kit

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DEIA250 | Influenza A H5N1 (Avian Flu) Hemagglutinin, HA ELISA Kit, 5 plates
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(1) Phosphorylation of TRIM28 Enhances the Expression of IFN-β and Proinflammatory Cytokines During HPAIV Infection of Human Lung Epithelial Cells.[TOP]

Pubmed ID :30323812
Publication Date : //
Human infection with highly pathogenic avian influenza viruses (HPAIV) is often associated with severe tissue damage due to hyperinduction of interferons and proinflammatory cytokines. The reasons for this excessive cytokine expression are still incompletely understood, which has hampered the development of efficient immunomodulatory treatment options. The host protein TRIM28 associates to the promoter regions of over 13,000 genes and is recognized as a genomic corepressor and negative immune regulator. TRIM28 corepressor activity is regulated by post-translational modifications, specifically phosphorylation of S473, which modulates binding of TRIM28 to the heterochromatin-binding protein HP1. Here, we identified TRIM28 as a key immune regulator leading to increased IFN-β and proinflammatory cytokine levels during infection with HPAIV. Using influenza A virus strains of the subtype H1N1 as well as HPAIV of subtypes H7N7, H7N9, and H5N1, we could demonstrate that strain-specific phosphorylation of TRIM28 S473 is induced by a signaling cascade constituted of PKR, p38 MAPK, and MSK1 in response to RIG-I independent sensing of viral RNA. Furthermore, using chemical inhibitors as well as knockout cell lines, our results suggest that phosphorylation of S473 facilitates a functional switch leading to increased levels of IFN-β, IL-6, and IL-8. In summary, we have identified TRIM28 as a critical factor controlling excessive expression of type I IFNs as well as proinflammatory cytokines during infection with H5N1, H7N7, and H7N9 HPAIV. In addition, our data indicate a novel mechanism of PKR-mediated IFN-β expression, which could lay the ground for novel treatment options aiming at rebalancing dysregulated immune responses during severe HPAIV infection.

Authors : Krischuns Tim, Günl Franziska, Henschel Lea, Binder Marco, Willemsen Joschka, Schloer Sebastian, Rescher Ursula, Gerlt Vanessa, Zimmer Gert, Nordhoff Carolin, Ludwig Stephan, Brunotte Linda,



(2) Dynamics of the 2004 avian influenza H5N1 outbreak in Thailand: The role of duck farming, sequential model fitting and control.[TOP]

Pubmed ID :30314780
Publication Date : //
The Highly Pathogenic Avian Influenza (HPAI) subtype H5N1 virus persists in many countries and has been circulating in poultry, wild birds. In addition, the virus has emerged in other species and frequent zoonotic spillover events indicate that there remains a significant risk to human health. It is crucial to understand the dynamics of the disease in the poultry industry to develop a more comprehensive knowledge of the risks of transmission and to establish a better distribution of resources when implementing control. In this paper, we develop a set of mathematical models that simulate the spread of HPAI H5N1 in the poultry industry in Thailand, utilising data from the 2004 epidemic. The model that incorporates the intensity of duck farming when assessing transmision risk provides the best fit to the spatiotemporal characteristics of the observed outbreak, implying that intensive duck farming drives transmission of HPAI in Thailand. We also extend our models using a sequential model fitting approach to explore the ability of the models to be used in "real time" during novel disease outbreaks. We conclude that, whilst predictions of epidemic size are estimated poorly in the early stages of disease outbreaks, the model can infer the preferred control policy that should be deployed to minimise the impact of the disease.

Authors : Retkute Renata, Jewell Chris P, Van Boeckel Thomas P, Zhang Geli, Xiao Xiangming, Thanapongtharm Weerapong, Keeling Matt, Gilbert Marius, Tildesley Michael J,



(3) Passive inhalation of dry powder influenza vaccine formulations completely protects chickens against H5N1 lethal viral challenge.[TOP]

Pubmed ID :30312742
Publication Date : //
Bird to human transmission of high pathogenicity avian influenza virus (HPAIV) poses a significant risk of triggering a flu pandemic in the human population. Therefore, vaccination of susceptible poultry during an HPAIV outbreak might be the best remedy to prevent such transmissions. To this end, suitable formulations and an effective mass vaccination method that can be translated to field settings needs to be developed. Our previous study in chickens has shown that inhalation of a non-adjuvanted dry powder influenza vaccine formulation during normal breathing results in partial protection against lethal influenza challenge. The aim of the present study was to improve the effectiveness of pulmonary vaccination by increasing the vaccine dose deposited in the lungs and by the use of suitable adjuvants. Two adjuvants, namely, Bacterium-like Particles (BLP) and Advax, were spray freeze dried with influenza vaccine into dry powder formulations. Delivery of dry formulations directly at the syrinx revealed that BLP and Advax had the potential to boost either systemic or mucosal immune responses or both. Upon passive inhalation of dry influenza vaccine formulations in an optimized set-up, BLP and Advax/BLP adjuvanted formulations induced significantly higher systemic immune responses than the non-adjuvanted formulation. Remarkably, all vaccinated animals not only survived a lethal influenza challenge, but also did not show any shedding of challenge virus except for two out of six animals in the Advax group. Overall, our results indicate that passive inhalation is feasible, effective and suitable for mass vaccination of chickens if it can be adapted to field settings.

Authors : Tomar Jasmine, Biel Carin, de Haan Cornelis A M, Rottier Peter J M, Petrovsky Nikolai, Frijlink Henderik W, Huckriede Anke, Hinrichs Wouter L J, Peeters Ben,



(4) Pathology of Clade 2.3.2.1 Avian Influenza Virus (H5N1) Infection in Quails and Ducks in Bangladesh.[TOP]

Pubmed ID :30303027
Publication Date : //
We performed pathological and molecular virological investigation of three outbreaks of highly pathogenic avian influenza (HPAI) in a quail farm and two duck farms of Mymensingh and Netrokona districts of Bangladesh in 2011. HPAI viruses of subtype H5N1 were detected from all the three outbreaks and phylogenetic analysis of HA gene sequence placed the viruses into clade 2.3.2.1. The outbreak in the quail farm was characterized by acute death with 100% mortality within two days. Marked haemorrhages and congestion with necrotic and inflammatory lesions in the respiratory tract, liver, pancreas and kidney were the major gross and histopathological lesions. In case of ducks, nervous signs were the remarkable clinical manifestations and the mortality was around 10%. No significant gross lesions were observed at necropsy. Non-purulent encephalitis with gliosis and neuronal degeneration was observed on histopathological examination. By immunohistochemistry viral antigen could be detected in different organs of both quails and ducks. This study records varying clinical and pathological manifestations of HPAI in ducks and quails following natural infection with the same strain of the virus.

Authors : Nooruzzaman Mohammed, Haque Md Enamul, Chowdhury Emdadul Haque, Islam Mohammad Rafiqul,



(5) AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization.[TOP]

Pubmed ID :30302282
Publication Date : //
Immune responses to inactivated vaccines against avian influenza are poor due in part to lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses of polyclonal antibody responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered in presence or absence of AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced antibody epitope diversity to viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine. Furthermore, AS03 promoted significant antibody affinity maturation to properly folded H5-HA1 (but not to HA2) domain, which correlated with neutralization titers against both vaccine and heterologous H5N1 strains. However, no increase in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition antibody titers. This study provides insight into the differential impacts of AS03 adjuvant on H5N1 vaccine-induced antibody responses that may help optimize vaccine platforms for future vaccines with improved protection against seasonal and pandemic influenza strains.

Authors : Khurana Surender, Coyle Elizabeth M, Manischewitz Jody, King Lisa R, Gao Jin, Germain Ronald N, Schwartzberg Pamela L, Tsang John S, Golding Hana, ,



(6) Fatal Avian Influenza A/H5N1 Infection in a 36-Week Pregnant Woman Survived by her Newborn - Soc Trang, Vietnam, 2012.[TOP]

Pubmed ID :30291769
Publication Date : //
Outbreaks of H5N1 Avian Influenza (AI) emerged in Indonesia, Thailand and Viet Nam during 2003- 2005. Its severe impact has been reported; the Food and Agriculture Organization (FAO) and World Bank (WB) estimated that Viet Nam lost up to 1.8% of GDP (1). Since then the country reported over 3000 H5N1 poultry outbreaks (2) and 127 human H5N1 cases and 64 dead. This article is protected by copyright. All rights reserved.

Authors : Le Tuan, Phan Lan, Nguyen Long, Nguyen Hieu, Ly Khanh, Ho Thien Ngan, Trinh Tung, Nguyen Tran Minh,



(7) Chickens Expressing IFIT5 Ameliorate Clinical Outcome and Pathology of Highly Pathogenic Avian Influenza and Velogenic Newcastle Disease Viruses.[TOP]

Pubmed ID :30271403
Publication Date : //
Innate antiviral immunity establishes first line of defense against invading pathogens through sensing their molecular structures such as viral RNA. This antiviral potential of innate immunity is mainly attributed to a myriad of IFN-stimulated genes (ISGs). Amongst well-characterized ISGs, we have previously shown that antiviral potential of chicken IFN-induced proteins with tetratricopeptides repeats 5 (chIFIT5) is determined by its interaction potential with 5'ppp containing viral RNA. Here, we generated transgenic chickens using avian sarcoma-leukosis virus (RCAS)-based gene transfer system that constitutively and stably express chIFIT5. The transgenic chickens infected with clinical dose (EID 10 for HPAIV and 10 EID for vNDV) of high pathogenicity avian influenza virus (HPAIV; H5N1) or velogenic strain of Newcastle disease virus (vNDV; Genotype VII) showed marked resistance against infections. While transgenic chickens failed to sustain a lethal dose of these viruses (EID 10 for HPAIV and 10 EID for vNDV), a delayed and lower level of clinical disease and mortality, reduced virus shedding and tissue damage was observed compared to non-transgenic control chickens. These observations suggest that stable expression of chIFIT5 alone is potentially insufficient in providing sterile protection against these highly virulent viruses; however, it is sufficient to ameliorate the clinical outcome of these RNA viruses. These findings propose the potential of innate immune genes in conferring genetic resistance in chickens against highly pathogenic and zoonotic viral pathogens causing sever disease in both animals and humans.

Authors : Rohaim Mohammed A, Santhakumar Diwakar, Naggar Rania F El, Iqbal Munir, Hussein Hussein A, Munir Muhammad,



(8) Longevity of adenovirus vector immunity in mice and its implications for vaccine efficacy.[TOP]

Pubmed ID :30266488
Publication Date : //
There is a high incidence of adenovirus (AdV) infection in humans due to the presence of more than 60 types of human adenoviruses (HAdVs). The majority of individuals are exposed to one or more HAdV types early in their lives, leading to the development of AdV type-specific neutralizing antibodies. Similarly, immunization or gene therapy with AdV vectors leads to immune responses to the AdV vector. This 'vector immunity' is a concern for AdV vector-based applications for vaccines or gene therapy, especially when the repeated administration of a vector is required. The objective of this investigation was to establish whether AdV neutralizing antibody titers decline sufficiently in a year to permit annual vaccination with the same AdV vector. Naïve or human adenoviral vector group C, type 5 (HAdV-C5)-primed mice were mock-inoculated (with PBS) or inoculated i.m. with 10 PFU of either HAd-GFP [HAdV-C5 vector expressing the green fluorescent protein (GFP)] to mimic the conditions for the first inoculation with an AdV vector-based vaccine. At 1, 3, 6, and 10 months post-HAd-GFP inoculation, naïve- or HAdV-primed animals were vaccinated i.m. with 10 PFU of HAd-H5HA [HAdV-C5 vector expressing hemagglutinin (HA) of H5N1 influenza virus]. There was a significant continual decrease in vector immunity titers with time, thereby leading to significant continual increases in the levels of HA-specific humoral and cell-mediated immune responses. In addition, significant improvement in protection efficacy against challenge with an antigenically heterologous H5N1 virus was observed in HAdV-primed animals at 6 months and onwards. These results indicate that the annual immunization with the same AdV vector may be effective due to a significant decline in vector immunity.

Authors : Sayedahmed Ekramy E, Kumari Rashmi, Shukla Shruti, Hassan Ahmed O, Mohammed Sulma I, York Ian A, Gangappa Shivaprakash, Sambhara Suryaprakash, Mittal Suresh K,



(9) The Multifaceted Zoonotic Risk of H9N2 Avian Influenza.[TOP]

Pubmed ID :30248906
Publication Date : //
Poultry-adapted H9N2 avian influenza viruses (AIVs) are commonly found in many countries in Asia, the Middle East, Africa, and Europe, and although classified as low pathogenic viruses, they are an economically important disease. Besides the importance of the disease in the poultry industry, some H9N2 AIVs are also known to be zoonotic. The disease in humans appears to cause primarily a mild upper respiratory disease, and doesn't cause or only rarely causes the severe pneumonia often seen with other zoonotic AIVs like H5N1 or H7N9. Serologic studies in humans, particularly in occupationally exposed workers, show a large number of people with antibodies to H9N2, suggesting infection is commonly occurring. Of the four defined H9N2 poultry lineages, only two lineages, the G1 and the Y280 lineages, are associated with human infections. Almost all of the viruses from humans have a leucine at position 226 (H3 numbering) of the hemagglutinin associated with a higher affinity of binding with α2,6 sialic acid, the host cell receptor most commonly found on glycoproteins in the human upper respiratory tract. For unknown reasons there has also been a shift in recent years of poultry viruses in the G1 and Y280 lineages to also having leucine instead of glutamine, the amino acid found in most avian viruses, at position 226. The G1 and Y280 poultry lineages because of their known ability to infect humans, the high prevalence of the virus in poultry in endemic countries, the lack of antibody in most humans, and the shift of poultry viruses to more human-like receptor binding makes these viruses a human pandemic threat. Increased efforts for control of the virus, including through effective vaccine use in poultry, is warranted for both poultry and public health goals.

Authors : Pusch Elizabeth A, Suarez David L,



(10) Lethal influenza A virus preferentially activates TLR3 and triggers a severe inflammatory response.[TOP]

Pubmed ID :30248373
Publication Date : //
The "cytokine storm" and excessive inflammation triggered by lethal avian influenza virus (IAV) are responsible for its high virulence and mortality. However, the molecular mechanism behind these effects is unclear. In this study, we used LA795 cells and a mouse model to assess the crucial role of TLR3 during infection with lethal avian influenza A virus and subsequent inflammation. The results showed that IAVs could replicate and proliferate well in LA795 cells and that the replication of H5N1 was more efficient than human H1N1 and lowly pathogenic avian H7N2 viruses. The TLR3 signaling pathways were activated preferentially in vitro and in vivo and a range of pro-inflammatory cytokines were released following H5N1 infection. RNAi and TLR3 knockout mice were used to validate the results. These results are the first to provide insight into the preferential involvement of TLR3 in lethal avian influenza A virus infection and inflammation compared with others such as human or lowly pathogenic avian influenza A viruses. The data will increase understanding of the pathogenesis of lethal avian influenza A virus infection and may help facilitate the development of novel therapeutic aids targeting TLR3 signaling pathways.

Authors : Huo Caiyun, Jin Yi, Zou Shumei, Qi Peng, Xiao Jin, Tian Haiyan, Wang Ming, Hu Yanxin,