#Preclinical evaluation of the efficacy of an #H5N8 #vaccine candidate (IDCDC-RG43A) in mouse and ferret models for #pandemic preparedness (Vaccine, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vaccine. 2018 Nov 27. pii: S0264-410X(18)31589-5. doi: 10.1016/j.vaccine.2018.11.064. [Epub ahead of print]

Preclinical evaluation of the efficacy of an H5N8 vaccine candidate (IDCDC-RG43A) in mouse and ferret models for pandemic preparedness.

Jeong JH1, Kim EH1, Lloren KKS1, Kwon JJ1, Kwon HI1, Ahn SJ1, Kim YI1, Choi WS1, Si YJ1, Lee OJ1, Han HJ2, Baek YH1, Song MS3, Choi YK4, Kim CJ5.

Author information: 1 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea. 2 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea; Research & Development Center, Green Cross Corporation, Yongin, Republic of Korea; Research & Development Center, Green Cross Wellbeing Corporation, Seongnam, Republic of Korea. 3 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea. Electronic address: songminsuk@chungbuk.ac.kr. 4 Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea. Electronic address: choiki55@chungbuk.ac.kr. 5 College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea. Electronic address: cjkim@cnu.ac.kr.

 

Abstract

Because H5N1 influenza viruses continuously threaten the public health, the WHO has prepared various clades of H5N1 mock-up vaccines as one of the measures for pandemic preparedness. The recent worldwide outbreak of H5Nx virus which belongs to clade 2.3.4.4 and of which H5N6 subtype belongs and already caused human infection also increases the need of pandemic vaccine for such novel emerging viruses. In this study, we evaluated the protective efficacy and immunogenicity of an egg-based and inactivated whole-virus H5N8 (IDCDC-RG43A) developed by CDC containing HA and NA gene of the parent virus A/gyrfalcon/Washington/41088-6/2014. Mice vaccinated two times elicited low to moderate antibody titer in varying amount of antigen doses against the homologous H5N8 vaccine virus and heterologous intra-clade 2.3.4.4 H5N6 (A/Sichuan/26221/2014) virus. Mice immunized with at least 3.0 µg/dose of IDCDC-RG43A with aluminum hydroxide adjuvant were completely protected from lethal challenge with the mouse-adapted H5N8 (A/Environment/Korea/ma468/2015, maH5N8) as well as cleared the viral replication in tissues including lung, brain, spleen, and kidney. Vaccinated ferrets induced high antibody titers against clade 2.3.4.4 H5N8/H5N6 viruses and the antibody showed high cross-reactivity to clade 2.2 H5N1 but not to clade 1 and 2.3.4 viruses as measured by hemagglutinin inhibition and serum neutralization assays. Furthermore, administration of the vaccine in ferrets resulted in attenuation of clinical disease signs and virus spread to peripheral organs including lung, spleen, and kidney from high dose challenge with maH5N8 virus. The protective and immunogenic characteristic of the candidate vaccine are essential attributes to be considered for further clinical trials as a pre-pandemic vaccine for a potential pandemic virus.

KEYWORDS: H5N8 pre-pandemic vaccine; Immunogenicity; Preclinical evaluation; Protective efficacy

PMID: 30502069 DOI: 10.1016/j.vaccine.2018.11.064

Keywords: Avian Influenza; Pandemic Influenza; Pandemic Preparedness; Vaccines; H5N1; H5N6; H5N8.

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T160A #mutation-induced deglycosylation at site 158 in #HA is a critical determinant of the dual #RB properties of clade 2.3.4.4 #H5NX subtype #avian #influenza viruses (Vet Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Microbiol. 2018 Apr;217:158-166. doi: 10.1016/j.vetmic.2018.03.018. Epub 2018 Mar 17.

T160A mutation-induced deglycosylation at site 158 in hemagglutinin is a critical determinant of the dual receptor binding properties of clade 2.3.4.4 H5NX subtype avian influenza viruses.

Gao R1, Gu M2, Liu K1, Li Q1, Li J1, Shi L1, Li X1, Wang X2, Hu J2, Liu X2, Hu S2, Chen S2, Peng D3, Jiao X3, Liu X4.

Author information: 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China. 2 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China. 3 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, Jiangsu 225009, China. 4 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu 225009, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou, Jiangsu 225009, China. Electronic address: xfliu@yzu.edu.cn.

 

Abstract

Most clade 2.3.4.4 H5NX subtype avian influenza viruses possess a T160A amino acid substitution in the hemagglutinin (HA) protein that has been shown to affect the receptor binding properties of a clade 2.3.4 H5N1 virus. However, the effect of this single site mutation on the HA backbone of clade 2.3.4.4 H5NX viruses remains unclear. In this study, two H5N6 field isolates possessing HA-160A with dual α-2,3 and α-2,6 receptor binding properties (Y6 virus) and HA-160T with α-2,3 receptor binding affinity (HX virus), respectively, were selected to generate HA mutants containing all of the internal genes from A/PR8/H1N1 virus for comparative investigation. We found that the Y6-P-160A and RHX-P-160A viruses each with 160A in the HA resulting in loss of glycosylation at site 158 exhibited binding to the two receptor types, whereas the RY6-P-160T and HX-P-160T viruses each with 160T in the HA displayed selective binding to α-2,3 receptors only. In addition, differences were noted in the replication of these four H5N6 recombinants in avian and mammalian cells, as well as in their pathogenicity in mice. The contribution of deglycosylation at site 158 to the acquisition of human-like receptors was further verified in H5N2, H5N5 and H5N8 reassortants. Therefore, we conclude that the lack of glycosylation at site 158 induced by the T160A mutation in HA is a critical determinant for the dual receptor binding properties of clade 2.3.4.4 H5NX viruses. This new insight may be helpful in assessing the pandemic potential of novel H5 isolates.

KEYWORDS: 158; Clade 2.3.4.4; Glycosylation; H5NX; Receptor

PMID: 29615249 DOI: 10.1016/j.vetmic.2018.03.018 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N2; H5N5; H5N6; H5N8; Reassortant Strain.

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White-Tailed Sea #Eagle (Haliaeetus albicilla) #DieOff Due to #Infection with Highly Pathogenic #Avian #Influenza Virus, Subtype #H5N8, in #Germany (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2018 Sep 7;10(9). pii: E478. doi: 10.3390/v10090478.

White-Tailed Sea Eagle (Haliaeetus albicilla) Die-Off Due to Infection with Highly Pathogenic Avian Influenza Virus, Subtype H5N8, in Germany.

Krone O1, Globig A2, Ulrich R3, Harder T4, Schinköthe J5, Herrmann C6, Gerst S7, Conraths FJ8, Beer M9.

Author information: 1 Department of Wildlife Diseases, Leibniz Institute for Zoo and Wildlife Research, 10315 Berlin, Germany. krone@izw-berlin.de. 2 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany. Anja.Globig@fli.de. 3 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany. Reiner.Ulrich@fli.de. 4 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany. Timm.Harder@fli.de. 5 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany. jan.schinkoethe@fli.de. 6 Agency for Environment, Nature Conservation, and Geology Mecklenburg-Western Pomerania, 18273 Güstrow, Germany. Christof.Herrmann@lung.mv-regierung.de. 7 Department of Diagnostic Investigation of Epizootics (LALLF), State Office for Agriculture, Food Safety, and Fishery, Mecklenburg-Western Pomerania, 18059 Rostock, Germany. sascha.gerst@lallf.mvnet.de. 8 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany. Franz.Conraths@fli.de. 9 Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany. Martin.Beer@fli.de.

 

Abstract

In contrast to previous incursions of highly pathogenic avian influenza (HPAIV) H5 viruses, H5N8 clade 2.3.4.4b viruses caused numerous cases of lethal infections in white-tailed sea eagles (Haliaeetus albicilla) affecting mainly young eagles (younger than five years of age) in Germany during winter 2016/2017. Until April 2017, 17 HPAIV H5N8-positive white-tailed sea eagles had been detected (three found alive and 14 carcasses) by real-time RT-PCR and partial nucleotide sequence analyses. Severe neurological clinical signs were noticed which were corroborated by immunohistopathology revealing mild to moderate, oligo- to multifocal necrotizing virus-induced polioencephalitis. Lethal lead (Pb) concentrations, a main factor of mortality in sea eagles in previous years, could be ruled out by atomic absorption spectrometry. HPAIV H5 clade 2.3.4.4b reportedly is the first highly pathogenic influenza virus known to induce fatal disease in European white-tailed see eagles. This virus strain may become a new health threat to a highly protected species across its distribution range in Eurasia. Positive cloacal swabs suggest that eagles can spread the virus with their faeces.

KEYWORDS: HPAIV H5N8 clade 2.3.4.4b; fatal infection; neurological symptoms; white-tailed sea eagle

PMID: 30205456 PMCID: PMC6163648 DOI: 10.3390/v10090478 [Indexed for MEDLINE]  Free PMC Article

Keywords: Avian Influenza; H5N8; Wild Birds; Germany.

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Highly pathogenic #avian #influenza #H5N8 Clade 2.3.4.4B virus in #Uganda, 2017 (Infect Genet Evol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infect Genet Evol. 2018 Oct 17. pii: S1567-1348(18)30508-2. doi: 10.1016/j.meegid.2018.10.010. [Epub ahead of print]

Highly pathogenic avian influenza H5N8 Clade 2.3.4.4B virus in Uganda, 2017.

Ndumu D1, Zecchin B2, Fusaro A2, Arinaitwe E1, Erechu R1, Kidega E1, Kayiwa J3, Muwanga E1, Kirumira M1, Kirembe G1, Lutwama J3, Monne I4.

Author information: 1 Directorate of Animal Resources, Ministry of Agriculture, Animal Industry and Fisheries (MAAIF), P.O. Box 513, Entebbe, Uganda. 2 Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell’Università, 10, 35020, Legnaro, Padova, Italy. 3 Uganda Virus Research Institute (UVRI), P. O. Box 49, Entebbe, Uganda. 4 Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell’Università, 10, 35020, Legnaro, Padova, Italy. Electronic address: imonne@izsvenezie.it.

 

Abstract

In early January 2017, outbreaks of H5N8 highly pathogenic avian influenza (HPAI) were reported for the first time in wild and domestic birds along the shores and on some islands of Lake Victoria, in central-southern Uganda. Our whole-genome phylogenetic analyses revealed that the H5N8 viruses recovered from the outbreak in Uganda belonged to genetic clade 2.3.4.4 group-B and clustered with viruses collected in 2017 in the Democratic Republic of the Congo and in West Africa. Our results suggested that infected migratory wild birds might have played a crucial role in the introduction of HPAI H5N8 into this region.

KEYWORDS: H5N8 subtype; Influenza A virus; Migratory wild birds; Phylogeny; Uganda

PMID: 30342095 DOI: 10.1016/j.meegid.2018.10.010

Keywords: Avian Influenza; H5N8; Poultry; Wild Birds; Uganda.

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#Development and comparison of two #H5N8 #influenza A #vaccine candidate strains (Arch Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Arch Virol. 2018 Oct 5. doi: 10.1007/s00705-018-4062-9. [Epub ahead of print]

Development and comparison of two H5N8 influenza A vaccine candidate strains.

Lee MS1,2, Jang EY1,3, Cho J1,3, Kim K1, Lee CH3, Yi H4.

Author information: 1 Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, 187, Osongsaengmyeong2-ro, Cheongju-si, 28159, Chungcheongbuk-do, Korea. 2 Department of Life Science and Technology, Pai Chai University, Daejeon, Korea. 3 Department of Microbiology, Chungbuk National University, Cheongju, Korea. 4 Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, 187, Osongsaengmyeong2-ro, Cheongju-si, 28159, Chungcheongbuk-do, Korea. msnef@naver.com.

 

Abstract

Avian influenza viruses circulating in birds have caused outbreaks of infection in poultry and humans, thereby threatening public health. Recently, a highly pathogenic avian influenza (HPAI) virus (H5N8) of clade 2.3.4.4 emerged in Korea and other countries and caused multiple outbreaks in domestic and wild birds, with concerns for human infection. To combat HPAI viral infections, novel vaccines are likely to be the most effective approach. Therefore, in this study, we generated H5N8 vaccine candidate viruses based on a Korean isolate (A/broiler duck/Korea/Buan2/2014). The vaccine candidate viruses were 2:6 reassortants expressing the two surface glycoproteins of A/broiler duck/Korea/Buan2/2014 on an A/Puerto Rico/8/34 (PR8) backbone generated by using an eight-plasmid-based reverse genetics system with or without replacement of the multi-basic amino acid cleavage motif (MBCM, a crucial pathogenic factor in HPAI virus) with a bi-basic amino acid cleavage motif (BBCM) in their HA. An H5N8 vaccine candidate virus containing the BBCM showed attenuated pathogenesis in embryonated eggs and exhibited less virulence in the infected mice compared with the wild H5N8 virus containing an MBCM. Vaccination with an inactivated preparation of the vaccine candidate virus protected mice from lethal H5N8 viral challenge. This is the first report of the development and evaluation of H5N8 vaccine strains (with an MBCM or BBCM) of HA clade 2.3.4.4 as vaccine candidates. Our findings suggest that H5N8 strains with a BBCM instead of an MBCM might be considered for H5N8 vaccine seed virus development or as a reference vaccine against H5N8 viral strains.

PMID: 30291503 DOI: 10.1007/s00705-018-4062-9

Keywords: Avian Influenza; H5N8; Vaccines.

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Multiple #adaptive #aminoacid #substitutions increase the #virulence of a wild #waterfowl-origin #reassortant #H5N8 #avian #influenza virus in mice (Virus Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virus Res. 2018 Jan 15;244:13-20. doi: 10.1016/j.virusres.2017.11.002. Epub 2017 Nov 4.

Multiple adaptive amino acid substitutions increase the virulence of a wild waterfowl-origin reassortant H5N8 avian influenza virus in mice.

Yu Z1, Cheng K2, Sun W3, Zhang X3, Xia X4, Gao Y5.

Author information: 1 Institute of Poultry Science, Shandong Academy of Agricultural Sciences, Jinan, 250023, China. Electronic address: zhijun0215@gmail.com. 2 Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China. 3 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China. 4 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. Electronic address: xiaxzh@cae.cn. 5 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China. Electronic address: gaoyuwei@gmail.com.

 

Abstract

A novel H5N8 highly pathogenic avian influenza virus (HPAIV) caused poultry outbreaks in the Republic of Korea in 2014. The novel H5N8 HPAIV has spread to Asia, Europe, and North America and caused great public concern from then on. Here, we generated mouse-adapted variants of a wild waterfowl-origin H5N8 HPAIV to identify adaptive mutants that confer enhanced pathogenicity in mammals. The mouse lethal doses (MLD50) of the mouse-adapted variants were reduced 31623-fold compared to the wild-type (WT) virus. Mouse-adapted variants displayed enhanced replication in vitro and in vivo, and expanded tissue tropism in mice. Sequence analysis revealed four amino acid substitutions in the PB2 (E627K), PA (F35S), HA (R227H), and NA (I462V) proteins. These data suggest that multiple amino acid substitutions collaboratively increase the virulence of a wild bird-origin reassortant H5N8 HPAIV and cause severe disease in mice.

KEYWORDS: Avian influenza virus; H5N8; Mice; Virulence; Wild waterfowl

PMID: 29113821 DOI: 10.1016/j.virusres.2017.11.002 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N6; H5N8; Animal Models; Reassortant Strain.

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Novel #reassortants of clade 2.3.4.4 #H5N6 highly pathogenic #avian #influenza viruses possessing genetic heterogeneity in Republic of #Korea in late 2017 (J Vet Sci., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Vet Sci. 2018 Aug 30. [Epub ahead of print]

Novel reassortants of clade 2.3.4.4 H5N6 highly pathogenic avian influenza viruses possessing genetic heterogeneity in Republic of Korea in late 2017.

Lee YN1, Cheon SH1, Kye SJ1, Lee EK1, Sagong M1, Heo GB1, Kang YM1, Cho HK1, Kim YJ1, Kang HM1, Lee MH1, Lee YJ1.

Author information: 1 Avian Influenza Research & Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea.

 

Abstract

Novel H5N6 highly pathogenic avian influenza viruses (HPAIVs) were isolated from duck farms and migratory bird habitats in South Korea in November-December 2017. Genetic analysis demonstrated that at least two genotypes of H5N6 were generated through reassortment between clade 2.3.4.4 H5N8 HPAIVs and Eurasian low pathogenic avian influenza virus in migratory birds in late 2017, suggesting frequent reassortment of clade 2.3.4.4 H5 HPAIVs, and highlighting the need for systematic surveillance in Eurasian breeding grounds.

KEYWORDS: H5N6; H5N8; clade 2.3.4.4; highly pathogenic avian influenza; reassortment

Keywords: Avian Influenza; H5N6; H5N8; Reassortant Strain; S. Korea.

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