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  1. Article: Inactivated Split MERS-CoV Antigen Prevents Lethal Middle East Respiratory Syndrome Coronavirus Infections in Mice.

    Seo, Heejeong / Jang, Yunyueng / Kwak, Dongmi

    Vaccines

    2024  Volume 12, Issue 4

    Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) causes fatal infections, with about 36% mortality in humans, and is endemic to the Middle East. MERS-CoV uses human dipeptidyl peptidase 4 (hDPP4) as a receptor for infection. Despite continued ... ...

    Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) causes fatal infections, with about 36% mortality in humans, and is endemic to the Middle East. MERS-CoV uses human dipeptidyl peptidase 4 (hDPP4) as a receptor for infection. Despite continued research efforts, no licensed vaccine is available for protection against this disease in humans. Therefore, this study sought to develop an inactivated fragmented MERS-CoV vaccine grown in Vero cells in an hDPP4-transgenic mouse model. Two-dose immunisation in mice with 15, 20, or 25 μg of spike proteins of inactivated split MERS-CoV antigens induced neutralising antibodies, with titres ranging from NT 80 to 1280. In addition, all immunised mice were completely protected, with no virus detection in tissues, weight loss, or mortality. The immunised splenocytes produced more cytokines that stimulate immune response (IFN-γ and TNF-α) than those that regulate it (IL-4 and IL-10). Taken together, the inactivated fragmented MERS-CoV vaccine is effective for the protection of mice against lethal MERS-CoV. Thus, the inactivated fragmented MERS-CoV vaccine warrants further testing in other hosts.
    Language English
    Publishing date 2024-04-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines12040436
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Protective Efficacy of Single-Dose Nasal Immunization with Cold-Adapted Live-Attenuated MERS-CoV Vaccine against Lethal MERS-CoV Infections in Mice.

    Seo, Heejeong / Jang, Yunyueng / Kwak, Dongmi

    Vaccines

    2023  Volume 11, Issue 8

    Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe diseases in humans. Camels act as intermediate hosts for MERS-CoV. Currently, no licensed vaccine is available for this virus. We have developed a potential candidate vaccine for MERS- ... ...

    Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe diseases in humans. Camels act as intermediate hosts for MERS-CoV. Currently, no licensed vaccine is available for this virus. We have developed a potential candidate vaccine for MERS-CoV using the cold adaptation method. We cultivated the vaccine in Vero cells at temperatures as low as 22 °C. This live-attenuated vaccine virus showed high attenuation levels in transgenic mice with the MERS-CoV human receptor, dipeptidyl peptidase 4 (DPP4) (K18-hDPP4). The inoculated K18-hDPP4 mice exhibited no clinical signs such as death or body weight loss. Furthermore, no traces of infectious virus were observed when the tissues (nasal turbinate, brain, lung, and kidney) of the K18-hDPP4 mice infected with the cold-adapted vaccine strain were tested. A single intranasal dose of the vaccine administered to the noses of the K18-hDPP4 mice provided complete protection. We did not observe any deaths, body weight loss, or viral detection in the tissues (nasal turbinate, brain, lung, and kidney). Based on these promising results, the developed cold-adapted, attenuated MERS-CoV vaccine strain could be one of the candidates for human and animal vaccines.
    Language English
    Publishing date 2023-08-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11081353
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: H5 cleavage-site peptide vaccine protects chickens from lethal infection by highly pathogenic H5 avian influenza viruses

    Jang, Yunyueng / Seo, Sang Heui

    Archives of virology. 2022 Jan., v. 167, no. 1

    2022  

    Abstract: Highly pathogenic H5Nx avian influenza viruses constantly threaten the poultry industry and humans and have pandemic potential. These viruses continuously evolve, requiring a universal vaccine to protect chickens from members of diverse clades. The ... ...

    Abstract Highly pathogenic H5Nx avian influenza viruses constantly threaten the poultry industry and humans and have pandemic potential. These viruses continuously evolve, requiring a universal vaccine to protect chickens from members of diverse clades. The purpose of this study was to develop an H5 cleavage-site peptide vaccine containing polybasic amino acids (RRRK) to completely protect chickens from H5N6, H5N8, and H5N1 avian influenza viruses. Chickens were immunized with various doses of a keyhole limpet hemocyanin (KLH)-conjugated H5 cleavage-site peptide vaccine containing RRRK. The effect of RRRK was evaluated by comparing the survival rates of chickens immunized with vaccines either containing or lacking RRRK. The ability of the RRRK-containing vaccine to confer long-term protective immunity was also assessed. We found that protection was dependent on the number of antigens in the vaccine containing RRRK. Chickens immunized intramuscularly with two doses of 5 μg of the vaccine containing RRRK were completely protected, but those immunized with fewer than two doses of 3 or 1 μg were not protected. Chickens immunized with the vaccine lacking RRRK were not protected, suggesting the importance of the polybasic amino acids in conferring immunity. Our results suggest that conserved H5 cleavage-site peptides with polybasic amino acids may be a potential universal vaccine to protect chickens from various emerging clades of H5Nx avian influenza viruses.
    Keywords avian influenza ; immunity ; keyhole limpet hemocyanin ; pandemic ; peptides ; poultry industry ; vaccines ; virology
    Language English
    Dates of publication 2022-01
    Size p. 67-75.
    Publishing place Springer Vienna
    Document type Article
    ZDB-ID 7491-3
    ISSN 1432-8798 ; 0304-8608
    ISSN (online) 1432-8798
    ISSN 0304-8608
    DOI 10.1007/s00705-021-05284-8
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: H5 cleavage-site peptide vaccine protects chickens from lethal infection by highly pathogenic H5 avian influenza viruses.

    Jang, Yunyueng / Seo, Sang Heui

    Archives of virology

    2021  Volume 167, Issue 1, Page(s) 67–75

    Abstract: Highly pathogenic H5Nx avian influenza viruses constantly threaten the poultry industry and humans and have pandemic potential. These viruses continuously evolve, requiring a universal vaccine to protect chickens from members of diverse clades. The ... ...

    Abstract Highly pathogenic H5Nx avian influenza viruses constantly threaten the poultry industry and humans and have pandemic potential. These viruses continuously evolve, requiring a universal vaccine to protect chickens from members of diverse clades. The purpose of this study was to develop an H5 cleavage-site peptide vaccine containing polybasic amino acids (RRRK) to completely protect chickens from H5N6, H5N8, and H5N1 avian influenza viruses. Chickens were immunized with various doses of a keyhole limpet hemocyanin (KLH)-conjugated H5 cleavage-site peptide vaccine containing RRRK. The effect of RRRK was evaluated by comparing the survival rates of chickens immunized with vaccines either containing or lacking RRRK. The ability of the RRRK-containing vaccine to confer long-term protective immunity was also assessed. We found that protection was dependent on the number of antigens in the vaccine containing RRRK. Chickens immunized intramuscularly with two doses of 5 μg of the vaccine containing RRRK were completely protected, but those immunized with fewer than two doses of 3 or 1 μg were not protected. Chickens immunized with the vaccine lacking RRRK were not protected, suggesting the importance of the polybasic amino acids in conferring immunity. Our results suggest that conserved H5 cleavage-site peptides with polybasic amino acids may be a potential universal vaccine to protect chickens from various emerging clades of H5Nx avian influenza viruses.
    MeSH term(s) Animals ; Chickens ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Humans ; Influenza A Virus, H5N1 Subtype ; Influenza Vaccines ; Influenza in Birds/prevention & control ; Vaccines, Subunit
    Chemical Substances Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines ; Vaccines, Subunit
    Language English
    Publishing date 2021-10-25
    Publishing country Austria
    Document type Journal Article
    ZDB-ID 7491-3
    ISSN 1432-8798 ; 0304-8608
    ISSN (online) 1432-8798
    ISSN 0304-8608
    DOI 10.1007/s00705-021-05284-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Evaluation of Efficacy of Oil Adjuvanted H5N6 Inactivated Vaccine against Highly Pathogenic H5N6 and H5N1 Influenza Viruses Infected Chickens.

    Kuruppuarachchi, Kuruppu Arachchillage Praboda Priyangi / Jang, Yunyueng / Seo, Sang Heui

    Frontiers in bioscience (Landmark edition)

    2022  Volume 27, Issue 9, Page(s) 268

    Abstract: Background: Over the last 20 years, circulating highly pathogenic (HP) Asian H5 subtype avian influenza viruses have caused global pandemics in poultry and sporadic infections in humans. Vaccines are a desirable solution to prevent viral infections in ... ...

    Abstract Background: Over the last 20 years, circulating highly pathogenic (HP) Asian H5 subtype avian influenza viruses have caused global pandemics in poultry and sporadic infections in humans. Vaccines are a desirable solution to prevent viral infections in poultry and reduce transmission to humans. Herein, we investigated the efficacy of an oil-adjuvanted inactivated H5N6 vaccine against highly pathogenic H5N6 and H5N1 influenza virus infections in chickens.
    Methods: The polybasic amino acid cleavage site depleted
    Results: The 384HA (n = 10) and 192HA (n = 5) antigen-immunized chickens showed 100% survival after lethal infections with homologous H5N6, and no virus shedding was observed from tracheal and cloacal routes. All chickens that received the 384HA vaccine survived the challenge of heterologous H5N1 after 4 weeks of immunization. The chickens that received the 384HA vaccine showed mean HI titers of 60 and 240 after 12 and 4 weeks of vaccination, respectively, against HP H5N6, whereas a mean HI titer of 80 was observed in sera collected 4 weeks after vaccination against HP H5N1.
    Conclusions: Our findings indicate that one dose of 384HA oil-adjuvanted inactivated H5N6 vaccine can induce a long-lasting immune response against both homologous H5N6 and heterologous H5N1 infections in chickens.
    MeSH term(s) Adjuvants, Immunologic/pharmacology ; Amino Acids ; Animals ; Chickens ; Formaldehyde ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza A virus ; Influenza Vaccines/genetics ; Influenza in Birds/prevention & control ; Influenza, Human ; Vaccines, Inactivated/genetics
    Chemical Substances Adjuvants, Immunologic ; Amino Acids ; Influenza Vaccines ; Vaccines, Inactivated ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2022-10-24
    Publishing country Singapore
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2704569-9
    ISSN 2768-6698 ; 2768-6698
    ISSN (online) 2768-6698
    ISSN 2768-6698
    DOI 10.31083/j.fbl2709268
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice.

    Kuruppuarachchi, Kuruppu Arachchillage Praboda Priyangi / Jang, Yunyueng / Seo, Sang Heui

    Frontiers in bioscience (Landmark edition)

    2022  Volume 27, Issue 11, Page(s) 316

    Abstract: Background: The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding the pathogenicity of these variants is a salient factor in the development of effective SARS-CoV-2 ... ...

    Abstract Background: The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding the pathogenicity of these variants is a salient factor in the development of effective SARS-CoV-2 therapeutics. This study aimed to compare the expression patterns of genes involved in immune responses in K18-hACE2 mice infected with the wild-type, Delta, and Omicron SARS-CoV-2 variants.
    Methods: K18-hACE2 mice were intranasally infected with either wild-type (B.1), Delta (B.1.617.2), or Omicron (B.1.1.529) variants. On day 6 post-infection, lung, brain, and kidney tissues were collected from each variant-infected group. The mRNA expression levels of 39 immune response genes in all three groups were compared by RT-qPCR. Viral titers were measured using the median tissue culture infectious dose (TCID50) assay and expressed as Log10 TCID50/0.1 g. The statistical significance of the differences in gene expression was determined by one-way analysis of variance (ANOVA) (alpha = 0.05).
    Results: The expression of toll-like receptors (TLRs) was upregulated in the lung and brain tissues of the wild-type- and Delta-infected groups but not in those of the Omicron-infected group. The highest expression of cytokines, including interleukin (
    Conclusions: Collectively, our findings revealed that the wild-type SARS-CoV-2 variant exhibited the highest pathogenicity, followed by the Delta variant, then the Omicron variant.
    Language English
    Publishing date 2022-11-23
    Publishing country Singapore
    Document type Journal Article
    ZDB-ID 2704569-9
    ISSN 2768-6698 ; 2768-6698
    ISSN (online) 2768-6698
    ISSN 2768-6698
    DOI 10.31083/j.fbl2711316
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection

    Sang Heui Seo / Yunyueng Jang

    Vaccines, Vol 8, Iss 584, p

    2020  Volume 584

    Abstract: A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of ... ...

    Abstract A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe a cold-adapted live-attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 °C/2020) developed by gradually adapting the growth of SARS-CoV-2 from 37 °C to 22 °C in Vero cells. This vaccine can be potentially administered to humans as a nasal spray. Its single dose strongly induced neutralising antibodies (titre > 640), cellular immunity, and mucosal IgA antibodies in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infections. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show body weight loss, death, or the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. These results demonstrate that the cold-adapted live attenuated SARS-CoV-2 vaccine we have developed may be a candidate SARS-CoV-2 vaccine for humans.
    Keywords SARS-CoV-2 ; live attenuated vaccine ; cold adaptation ; Medicine ; R ; covid19
    Subject code 572
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Age-Dependent Lethality in Ducks Caused by Highly Pathogenic H5N6 Avian Influenza Virus.

    Jang, Yunyueng / Seo, Sang Heui

    Viruses

    2020  Volume 12, Issue 6

    Abstract: Ducks show notably higher resistance to highly pathogenic avian influenza viruses as compared to chickens. Here, we studied the age-dependent susceptibility in ducks to the infections caused by highly pathogenic avian influenza viruses. We intranasally ... ...

    Abstract Ducks show notably higher resistance to highly pathogenic avian influenza viruses as compared to chickens. Here, we studied the age-dependent susceptibility in ducks to the infections caused by highly pathogenic avian influenza viruses. We intranasally infected ducks aged 1, 2, 4, and 8 weeks with highly pathogenic H5N6 avian influenza viruses isolated in South Korea in 2016. All the 1-and 2-week-old ducks died after infection, 20% of 3-week-old ducks died, and from the ducks aged 4 and 8 weeks, all of them survived. We performed microarray analysis and quantitative real-time PCR using total RNA isolated from the lungs of infected 2- and 4-week-old ducks to determine the mechanism underlying the age-dependent susceptibility to highly pathogenic avian influenza virus. Limited genes were found to be differentially expressed between the lungs of 2- and 4-week-old ducks. Cell damage-related genes, such as CIDEA and ND2, and the immune response-related gene NR4A3 were notably induced in the lungs of infected 2-week-old ducks compared to those in the lungs of infected 4-week-old ducks.
    MeSH term(s) Age Factors ; Animals ; Ducks/virology ; Gene Expression ; Gene Expression Regulation, Viral ; Influenza A virus/pathogenicity ; Influenza in Birds/mortality ; Influenza in Birds/virology ; Lung/metabolism ; Lung/virology ; Oligonucleotide Array Sequence Analysis ; Poultry Diseases/mortality ; Poultry Diseases/virology ; Real-Time Polymerase Chain Reaction ; Viral Load
    Language English
    Publishing date 2020-05-29
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v12060591
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Cold-Adapted Live Attenuated SARS-Cov-2 Vaccine Completely Protects Human ACE2 Transgenic Mice from SARS-Cov-2 Infection.

    Seo, Sang Heui / Jang, Yunyueng

    Vaccines

    2020  Volume 8, Issue 4

    Abstract: A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of ... ...

    Abstract A safe and effective vaccine that can provide herd immunity against severe acute respiratory syndrome coronavirus (SARS-CoV-2) is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live, attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe a cold-adapted live-attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22 °C/2020) developed by gradually adapting the growth of SARS-CoV-2 from 37 °C to 22 °C in Vero cells. This vaccine can be potentially administered to humans as a nasal spray. Its single dose strongly induced neutralising antibodies (titre > 640), cellular immunity, and mucosal IgA antibodies in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infections. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show body weight loss, death, or the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. These results demonstrate that the cold-adapted live attenuated SARS-CoV-2 vaccine we have developed may be a candidate SARS-CoV-2 vaccine for humans.
    Keywords covid19
    Language English
    Publishing date 2020-10-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines8040584
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Gene expression pattern differences in primary human pulmonary epithelial cells infected with MERS-CoV or SARS-CoV-2.

    Jang, Yunyueng / Seo, Sang Heui

    Archives of virology

    2020  Volume 165, Issue 10, Page(s) 2205–2211

    Abstract: Coronaviruses such as MERS-CoV and SARS-CoV-2 infect the human respiratory tract and can cause severe pneumonia. Disease severity and outcomes are different for these two infections: the human mortality rate for MERS-CoV and SARS-CoV-2 is over 30% and ... ...

    Abstract Coronaviruses such as MERS-CoV and SARS-CoV-2 infect the human respiratory tract and can cause severe pneumonia. Disease severity and outcomes are different for these two infections: the human mortality rate for MERS-CoV and SARS-CoV-2 is over 30% and less than 10%, respectively. Here, using microarray assay, we analyzed the global alterations in gene expression induced by MERS-CoV or SARS-CoV-2 infections in primary human pulmonary epithelial cells. Overall, the number of differentially expressed genes was higher in human lung cells infected with MERS-CoV than in cells with SARS-CoV-2. Out of 44,556 genes analyzed, 127 and 50 were differentially expressed in cells infected with MERS-CoV and SARS-CoV-2, respectively (> 2-fold increase, compared to uninfected cells). Of these, only eight genes, including the one coding for CXCL8, were similarly modulated (upregulated or downregulated) by the two coronaviruses. Importantly, these results were virus-specific and not conditioned by differences in viral load, and viral growth curves were similar in human lung cells infected with both viruses. Our results suggest that these distinct gene expression profiles, detected early after infection by these two coronaviruses, may help us understand the differences in clinical outcomes of MERS-CoV and SARS-CoV-2 infections.
    MeSH term(s) Betacoronavirus/pathogenicity ; COVID-19 ; Cells, Cultured ; Chemokine CXCL6/genetics ; Coronavirus Infections/genetics ; Coronavirus Infections/virology ; Down-Regulation ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Gene Expression Profiling ; Host Microbial Interactions/genetics ; Humans ; Interleukin-8/genetics ; Lung/metabolism ; Lung/virology ; Middle East Respiratory Syndrome Coronavirus/pathogenicity ; Pandemics ; Pneumonia, Viral/genetics ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Species Specificity ; Up-Regulation
    Chemical Substances CXCL6 protein, human ; CXCL8 protein, human ; Chemokine CXCL6 ; Interleukin-8
    Keywords covid19
    Language English
    Publishing date 2020-07-10
    Publishing country Austria
    Document type Comparative Study ; Journal Article
    ZDB-ID 7491-3
    ISSN 1432-8798 ; 0304-8608
    ISSN (online) 1432-8798
    ISSN 0304-8608
    DOI 10.1007/s00705-020-04730-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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