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Article ; Online: Protection of SPF Chickens by H9N2 Y439 and G1 Lineage Vaccine against Homologous and Heterologous Viruses

Hyun-Kyu Cho / Yong-Myung Kang / Mingeun Sagong / Juhun Kim / Hyunjun Kim / Sungjun An / Youn-Jeong Lee / Hyun-Mi Kang

Vaccines, Vol 11, Iss 538, p

2023 Volume 538

Abstract: Prior to the identification of low pathogenic avian influenza H9N2 viruses belonging to the Y280 lineage in 2020, Y439 lineage viruses had been circulating in the Republic of Korea since 1996. Here, we developed a whole inactivated vaccine (vac564) by ... ...

Abstract	Prior to the identification of low pathogenic avian influenza H9N2 viruses belonging to the Y280 lineage in 2020, Y439 lineage viruses had been circulating in the Republic of Korea since 1996. Here, we developed a whole inactivated vaccine (vac564) by multiple passage of Y439 lineage viruses and then evaluated immunogenicity and protective efficacy in specific-pathogen-free chickens. We found that LBM564 could be produced at high yield in eggs (10 8.4 EID 50 /0.1 mL; 1024 hemagglutinin units) and was immunogenic (8.0 ± 1.2 log 2 ) in chickens. The vaccine showed 100% inhibition of virus in the cecal tonsil with no viral shedding detected in either oropharyngeal or cloacal swabs after challenge with homologous virus. However, it did not induce effective protection against challenge with heterologous virus. An imported commercial G1 lineage vaccine inhibited viral replication against Y280 and Y439 lineage viruses in major tissues, although viral shedding in oropharyngeal and cloacal swabs was observed up until 5 dpi after exposure to both challenge viruses. These results suggest that a single vaccination with vac564 could elicit immune responses, showing it to be capable of protecting chickens against the Y439 lineage virus. Thus, our results suggest the need to prepare suitable vaccines for use against newly emerging and re-emerging H9N2 viruses.
Keywords	vaccine ; avian influenza ; H9N2 ; protection ; multiple passage ; Medicine ; R
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Updating the National Antigen Bank in Korea

Yong-Myung Kang / Hyun-Kyu Cho / Sung-Jun An / Hyun-Jun Kim / Youn-Jeong Lee / Hyun-Mi Kang

Vaccines, Vol 10, Iss 1860, p

Protective Efficacy of Synthetic Vaccine Candidates against H5Nx Highly Pathogenic Avian Influenza Viruses Belonging to Clades 2.3.2.1 and 2.3.4.4

2022 Volume 1860

Abstract: Since 2018, Korea has been building an avian influenza (AI) national antigen bank for emergency preparedness; this antigen bank is updated every 2 years. To update the vaccine strains in the antigen bank, we used reverse genetics technology to develop ... ...

Abstract	Since 2018, Korea has been building an avian influenza (AI) national antigen bank for emergency preparedness; this antigen bank is updated every 2 years. To update the vaccine strains in the antigen bank, we used reverse genetics technology to develop two vaccine candidates against avian influenza strains belonging to clades 2.3.2.1d and 2.3.4.4h, and then evaluated their immunogenicity and protective efficacy in SPF chickens challenged with H5 viruses. The two vaccine candidates, named rgCA2/2.3.2.1d and rgES3/2.3.4.4h, were highly immunogenic, with hemagglutination inhibition (HI) titers of 8.2–9.3 log 2 against the vaccine strain, and 7.1–7.3 log 2 against the lethal challenge viruses (in which the HA genes shared 97% and 95.4% homology with that of rgCA2/2.3.2.1d and rgES3/2.3.4.4h, respectively). A full dose of each vaccine candidate provided 100% protection against the challenge viruses, with a reduction in clinical symptoms and virus shedding. A 1/10 dose provided similar levels of protection, whereas a 1/100 dose resulted in mortality and virus shedding by 7 dpi. Moreover, immunity induced by the two vaccines was long lasting, with HI titers of >7 log 2 against the vaccine strain remaining after 6 months. Thus, the two vaccine candidates show protective efficacy and can be used to update the AI national antigen bank.
Keywords	high pathogenic avian influenza ; synthesis of HA ; vaccine candidates ; antigen bank ; SPF chicken ; Medicine ; R
Subject code	630
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Evolution, Transmission, and Pathogenicity of High Pathogenicity Avian Influenza Virus A (H5N8) Clade 2.3.4.4, South Korea, 2014–2016

Yoon-Gi Baek / Yu-Na Lee / Yu-Ri Park / David H. Chung / Jung-Hoon Kwon / Young-Jae Si / Gyeong-Beom Heo / Youn-Jeong Lee / Dong-Hun Lee / Eun-Kyoung Lee

Frontiers in Veterinary Science, Vol

2022 Volume 9

Abstract: During 2014–2016, clade 2.3.4.4 H5N8 high pathogenicity avian influenza virus (HPAIV) caused the largest known avian influenza epidemic in South Korea. Based on data from earlier H5N8 outbreaks, primitive H5N8 virus in South Korea was classified into ... ...

Abstract	During 2014–2016, clade 2.3.4.4 H5N8 high pathogenicity avian influenza virus (HPAIV) caused the largest known avian influenza epidemic in South Korea. Based on data from earlier H5N8 outbreaks, primitive H5N8 virus in South Korea was classified into five subgroups: C1, C2, C3, C4, and C5. The present study investigated the pathogenic and molecular epidemiologic characteristics of H5N8 viruses obtained from 388 cases of poultry farms and 85 cases of wild bird infections in South Korea during 2014–2016. Representative viruses of subgroups C1, C2, and C4 showed significant pathobiological differences in specific pathogen-free (SPF) chickens, with the H1731 (C1) virus showing substantially lower infectivity, transmissibility, and pathogenicity than the H2102 (C2) and H1924 (C4) viruses. Full genome sequence analysis showed the number of mutations that significantly increased in domestic duck-origin H5N8 HPAIVs compared to the viruses from gallinaceous poultry. These differences may have been due to the long-term circulation of viruses in domestic duck farms. The same mutations, at positions 219 and 757 of PB1, independently evolving in the C0, C1, and C2 subgroups may have been positively selected, resulting in convergent evolution at the amino acid level. Bayesian discrete trait phylodynamic analysis (DTA) indicated multiple introductions of H5N8 HPAIV from wild birds into domestic poultry in various regions in South Korea. Following initial viral introduction into domestic duck farms in the western part of Korea, domestic ducks played a major role in viral transmission and maintenance. These findings highlight the need for continued genomic surveillance and pathobiological characterization of HPAIV in birds. Enhanced biosecurity in poultry farms should be implemented to prevent the introduction, maintenance, and spread of HPAIV.
Keywords	HPAI ; H5N8 ; pathogenesis ; selection pressure ; phylodynamic analysis ; Veterinary medicine ; SF600-1100
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Rank orders of mammalian pathogenicity-related PB2 mutations of avian influenza A viruses

Chung-Young Lee / Se-Hee An / Jun-Gu Choi / Youn-Jeong Lee / Jae-Hong Kim / Hyuk-Joon Kwon

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 13

Abstract: Abstract The PB2 gene is one of the key determinants for the mammalian adaptation of avian influenza A viruses (IAVs). Although mammalian pathogenicity-related mutations (MPMs) in PB2 genes were identified in different genetic backgrounds of avian IAVs, ... ...

Abstract	Abstract The PB2 gene is one of the key determinants for the mammalian adaptation of avian influenza A viruses (IAVs). Although mammalian pathogenicity-related mutations (MPMs) in PB2 genes were identified in different genetic backgrounds of avian IAVs, the relative effects of single or multiple mutations on viral fitness could not be directly compared. Furthermore, their mutational steps during mammalian adaptation had been unclear. In this study, we collectively compared the effects of individual and combined MPMs on viral fitness and determined their rank orders using a prototypic PB2 gene. Early acquired mutations may determine the function and potency of subsequent mutations and be important for recruiting multiple, competent combinations of MPMs. Higher mammalian pathogenicity was acquired with the greater accumulation of MPMs. Thus, the rank orders and the prototypic PB2 gene may be useful for predicting the present and future risks of PB2 genes of avian and mammalian IAVs.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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Article ; Online: Selection of an Optimal Recombinant Egyptian H9N2 Avian Influenza Vaccine Strain for Poultry with High Antigenicity and Safety

Se-Hee An / Seung-Eun Son / Jin-Ha Song / Seung-Min Hong / Chung-Young Lee / Nak-Hyung Lee / Young-Ju Jeong / Jun-Gu Choi / Youn-Jeong Lee / Hyun-Mi Kang / Kang-Seuk Choi / Hyuk-Joon Kwon

Vaccines, Vol 10, Iss 162, p

2022 Volume 162

Abstract: For the development of an optimized Egyptian H9N2 vaccine candidate virus for poultry, various recombinant Egyptian H9N2 viruses generated by a PR8-based reverse genetics system were compared in terms of their productivity and biosafety since Egyptian ... ...

Abstract	For the development of an optimized Egyptian H9N2 vaccine candidate virus for poultry, various recombinant Egyptian H9N2 viruses generated by a PR8-based reverse genetics system were compared in terms of their productivity and biosafety since Egyptian H9N2 avian influenza viruses already possess mammalian pathogenicity-related mutations in the hemagglutinin (HA), neuraminidase (NA), and PB2 genes. The Egyptian HA and NA genes were more compatible with PR8 than with H9N2 AIV (01310) internal genes, and the 01310-derived recombinant H9N2 strains acquired the L226Q reverse mutation in HA after passages in eggs. Additionally, the introduction of a strong promoter at the 3′-ends of PB2 and PB1 genes induced an additional mutation of P221S. When recombinant Egyptian H9N2 viruses with intact or reverse mutated HA (L226Q and P221S) and NA (prototypic 2SBS) were compared, the virus with HA and NA mutations had high productivity in ECES but was lower in antigenicity when used as an inactivated vaccine due to its high binding affinity into non-specific inhibitors in eggs. Finally, we substituted the PB2 gene of PR8 with 01310 to remove the replication ability in mammalian hosts and successfully generated the best recombinant vaccine candidate in terms of immunogenicity, antigenicity, and biosafety.
Keywords	avian influenza virus ; H9N2 ; genetic evolution ; mammalian non-pathogenicity ; recombinant vaccine strain ; Medicine ; R
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Isolation and characterization of low pathogenic H7N7 avian influenza virus from a red-crowned crane in a zoo in South Korea

Young-Jae Si / Yu-Na Lee / Sun-Ha Cheon / Yu-Ri Park / Yoon-Gi Baek / Soo-Jeong Kye / Myoung-Heon Lee / Youn-Jeong Lee

BMC Veterinary Research, Vol 16, Iss 1, Pp 1-

2020 Volume 6

Abstract: Abstract Background South Korea conducts annual national surveillance programs to detect avian influenza (AI) in domestic poultry, live bird markets, and wild birds. In March 2017, an AIV was isolated from fecal samples in an outdoor aviary flight cage ... ...

Abstract	Abstract Background South Korea conducts annual national surveillance programs to detect avian influenza (AI) in domestic poultry, live bird markets, and wild birds. In March 2017, an AIV was isolated from fecal samples in an outdoor aviary flight cage in a zoo in Korea. Results Nucleotide sequencing identified the isolate as low pathogenic avian influenza virus (LPAIV) H7N7, and DNA barcoding analysis identified the host species as red-crowned crane. This isolate was designated A/red-crowned crane/Korea/H1026/2017 (H7N7). Genetic analysis and gene constellation analysis revealed that A/red-crowned crane/Korea/H1026/2017 (H7N7) showed high similarity with four H7N7 LPAIVs isolated from wild bird habitats in Seoul and Gyeonggi in early 2017. Conclusions Considering the genetic similarity and similar collection dates of the viruses, and the fact that zoo bird cages are vulnerable to AIV, it is likely that fecal contamination from wild birds might have introduced LPAIV H7N7 into the red-crowned crane at the zoo. Therefore, our results emphasize that enhanced biosecurity measures should be employed during the wild bird migration season, and that continued surveillance should be undertaken to prevent potential threats to avian species in zoos and to humans.
Keywords	AI surveillance ; Biosecurity measure ; Genetic analysis ; H7N7 ; LPAI in a zoo ; Veterinary medicine ; SF600-1100
Subject code	590
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic characteristics and pathogenesis of H5 low pathogenic avian influenza viruses from wild birds and domestic ducks in South Korea

Yu-Na Lee / Dong-Hun Lee / Sun-Ha Cheon / Yu-Ri Park / Yoon-Gi Baek / Young-Jae Si / Soo-Jeong Kye / Eun-Kyoung Lee / Gyeong-Beom Heo / You-Chan Bae / Myoung-Heon Lee / Youn-Jeong Lee

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract H5 and H7 subtypes of low pathogenic avian influenza viruses (LPAIVs) can mutate to highly pathogenic forms and are therefore subject to stringent controls. We characterized H5 LPAIVs isolated from wild-bird habitats and duck farms in South ... ...

Abstract	Abstract H5 and H7 subtypes of low pathogenic avian influenza viruses (LPAIVs) can mutate to highly pathogenic forms and are therefore subject to stringent controls. We characterized H5 LPAIVs isolated from wild-bird habitats and duck farms in South Korea from 2010 to 2017. Through nationwide active surveillance for AIVs, 59 H5 LPAIVs were isolated from wild-bird habitats (a mean annual rate of 5.3% of AIV isolations). In 2015, one LPAI H5N3 strain was isolated on a duck farm. Phylogenetic analysis revealed that the hemagglutinin (HA) gene of H5 isolates belonged to the Eurasian lineage, classified into three subgroups (HA-II, HA-III, and HA-IV). The H5 LPAIVs of the HA-III and HA-IV subgroups appeared in 2015 and 2017 in unusually high proportions (13.1% and 14.4%, respectively). In gene-constellation analysis, H5 LPAIVs isolated from 2015 to 2017 constituted ≥ 35 distinct genotypes, representing high levels of genetic diversity. Representative strains of three HA subgroups replicated restrictively in specific-pathogen-free chickens. Among the 11 isolates that were tested, 10 infected and replicated in mice without prior adaptation. The frequency of recent H5 LPAIV isolates with high genetic diversity indicates the importance of continued surveillance in both wild birds and poultry to monitor genetic and pathobiological changes.
Keywords	Medicine ; R ; Science ; Q
Subject code	590
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Improvement of PR8-Derived Recombinant Clade 2.3.4.4c H5N6 Vaccine Strains by Optimization of Internal Genes and H103Y Mutation of Hemagglutinin

Se-Hee An / Seung-Min Hong / Seung-Eun Son / Jin-Ha Song / Chung-Young Lee / Jun-Gu Choi / Youn-Jeong Lee / Jei-Hyun Jeong / Jun-Beom Kim / Chang-Seon Song / Jae-Hong Kim / Kang-Seuk Choi / Hyuk-Joon Kwon

Vaccines, Vol 8, Iss 781, p

2020 Volume 781

Abstract: Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant ... ...

Abstract	Clade 2.3.4.4c H5N6 avian influenza A viruses (AIVs) may have originally adapted to infect chickens and have caused highly pathogenic avian influenza (HPAI) in poultry and human fatalities. Although A/Puerto Rico/8/1934 (H1N1) (PR8)-derived recombinant clade 2.3.4.4c H5N6 vaccine strains have been effective in embryonated chicken eggs-based vaccine production system, they need to be improved in terms of immunogenicity and potential mammalian pathogenicity. We replaced the PB2 gene alone or the PB2 (polymerase basic protein 2), NP (nucleoprotein), M (matrix protein) and NS (non-structural protein) genes together in the PR8 strain with corresponding genes from AIVs with low pathogenicity to remove mammalian pathogenicity and to match CD8+ T cell epitopes with contemporary HPAI viruses, respectively, without loss of viral fitness. Additionally, we tested the effect of the H103Y mutation of hemagglutinin (HA) on antigen productivity, mammalian pathogenicity and heat/acid stability. The replacement of PB2 genes and the H103Y mutation reduced the mammalian pathogenicity but increased the antigen productivity of the recombinant vaccine strains. The H103Y mutation increased heat stability but unexpectedly decreased acid stability, probably resulting in increased activation pH for HA. Interestingly, vaccination with inactivated recombinant virus with replaced NP, M and NS genes halted challenge virus shedding earlier than the recombinant vaccine without internal genes replacement. In conclusion, we successfully generated recombinant clade 2.3.4.4c H5N6 vaccine strains that were less pathogenic to mammals and more productive and heat stable than conventional PR8-derived recombinant strains by optimization of internal genes and the H103Y mutation of HA.
Keywords	clade 2.3.4.4c H5N6 vaccine ; antigen productivity ; T cell epitopes ; heat/acid stability ; Medicine ; R
Subject code	570
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: H13 influenza viruses in wild birds have undergone genetic and antigenic diversification in nature

Wang, Zu-Jyun / Hiroshi Kida / Keita Matsuno / Lam Thanh Nguyen / Masatoshi Okamatsu / Richard Webby / Scott Krauss / Takahiro Hiono / Yoshihiro Sakoda / Youn-Jeong Lee / Yuto Kikutani

Virus genes. 2018 Aug., v. 54, no. 4

2018

Abstract: Among 16 haemagglutinin (HA) subtypes of avian influenza viruses (AIVs), H13 AIVs have rarely been isolated in wild waterfowl. H13 AIVs cause asymptomatic infection and are maintained mainly in gull and tern populations; however, the recorded antigenic ... ...

Abstract	Among 16 haemagglutinin (HA) subtypes of avian influenza viruses (AIVs), H13 AIVs have rarely been isolated in wild waterfowl. H13 AIVs cause asymptomatic infection and are maintained mainly in gull and tern populations; however, the recorded antigenic information relating to the viruses has been limited. In this study, 2 H13 AIVs, A/duck/Hokkaido/W345/2012 (H13N2) and A/duck/Hokkaido/WZ68/2012 (H13N2), isolated from the same area in the same year in our surveillance, were genetically and antigenically analyzed with 10 representative H13 strains including a prototype strain, A/gull/Maryland/704/1977 (H13N6). The HA genes of H13 AIVs were phylogenetically divided into 3 groups (I, II, and III). A/duck/Hokkaido/W345/2012 (H13N2) was genetically classified into Group III. This virus was distinct from a prototype strain, A/gull/Maryland/704/1977 (H13N6), and the virus, A/duck/Hokkaido/WZ68/2012 (H13N2), both belonging to Group I. Antigenic analysis indicated that the viruses of Group I were antigenically closely related to those of Group II, but distinct from those of Group III, including A/duck/Hokkaido/W345/2012 (H13N2). In summary, our study indicates that H13 AIVs have undergone antigenic diversification in nature.
Keywords	ducks ; genes ; hemagglutinins ; Influenza A virus ; monitoring ; phylogeny ; prototypes ; viruses ; waterfowl ; wild birds
Language	English
Dates of publication	2018-08
Size	p. 543-549.
Publishing place	Springer US
Document type	Article
ZDB-ID	639496-6
ISSN	1572-994X ; 0920-8569
ISSN (online)	1572-994X
ISSN	0920-8569
DOI	10.1007/s11262-018-1573-0
Database	NAL-Catalogue (AGRICOLA)

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Article: Novel mutations in avian PA in combination with an adaptive mutation in PR8 NP exacerbate the virulence of PR8-derived recombinant influenza A viruses in mice

Lee, Chung-Young / Hyuk-Joon Kwon / Ilhwan Kim / Jae-Hong Kim / Jun-Gu Choi / Se-Hee An / Youn-Jeong Lee

Veterinary microbiology. 2018 July, v. 221

2018

Abstract: The polymerase complex of the low-pathogenic avian influenza virus [A/chicken/Korea/KBNP-0028/2000] (0028) has previously been characterized, and novel amino acid residues present in the polymerase acidic protein (PA) that likely contribute to ... ...

Abstract	The polymerase complex of the low-pathogenic avian influenza virus [A/chicken/Korea/KBNP-0028/2000] (0028) has previously been characterized, and novel amino acid residues present in the polymerase acidic protein (PA) that likely contribute to pathogenicity toward mammals have been identified. In the present study, our aims were to generate A/Puerto Rico/8/34 (PR8)-derived recombinant viruses containing the 0028-PA gene with a single amino acid mutation and to test their pathogenicity and replication ability. We found that the recombinant viruses acquired additional single mutations in the nucleoprotein (NP). Because the additional mutations in NP did not affect viral pathogenicity, but rather attenuated viral replication and polymerase activity, the incompatibility of the avian PA gene within the PR8 backbone may have induced an adaptive mutation in NP. To minimize the differences due to NP mutations, we generated 0028-PA mutants with an E375G mutation, not affecting viral replication and pathogenicity, in the NP gene. The PR8-PA(0028)-E684G mutant showed significantly higher viral replication in mammalian cells as compared to PR8-PA(0028) and led to 100% mortality in mice, with significantly increased interferon β expression. Thus, the E684G mutation in the PA gene may play an important role in viral pathogenicity in mice by increasing viral replication and the host immune response.
Keywords	amino acids ; enzyme activity ; genes ; immune response ; Influenza A virus ; interferons ; mice ; mortality ; mutants ; mutation ; nucleoproteins ; virulence ; virus replication ; viruses
Language	English
Dates of publication	2018-07
Size	p. 114-121.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
DOI	10.1016/j.vetmic.2018.05.026
Database	NAL-Catalogue (AGRICOLA)

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