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  1. Article ; Online: Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size.

    Fong, Carol Ho-Yan / Lu, Lu / Chen, Lin-Lei / Yeung, Man-Lung / Zhang, Anna Jinxia / Zhao, Hanjun / Yuen, Kwok-Yung / To, Kelvin Kai-Wang

    iScience

    2022  Volume 25, Issue 4, Page(s) 104037

    Abstract: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of ... ...

    Abstract The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.
    Language English
    Publishing date 2022-03-06
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways.

    Yang, Dong / Chan, Jasper Fuk-Woo / Yoon, Chaemin / Luk, Tsz-Yat / Shuai, Huiping / Hou, Yuxin / Huang, Xiner / Hu, Bingjie / Chai, Yue / Yuen, Terrence Tsz-Tai / Liu, Yuanchen / Zhu, Tianrenzheng / Liu, Huan / Shi, Jialu / Wang, Yang / He, Yixin / Sit, Ko-Yung / Au, Wing-Kuk / Zhang, Anna Jinxia /
    Yuan, Shuofeng / Zhang, Bao-Zhong / Huang, Yao-Wei / Chu, Hin

    Journal of medical virology

    2024  Volume 96, Issue 2, Page(s) e29472

    Abstract: Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we ... ...

    Abstract Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNβ treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.
    MeSH term(s) Humans ; SARS-CoV-2/metabolism ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; COVID-19 ; Virus Replication ; Lung ; Interferons ; Epithelial Cells ; Antiviral Agents/pharmacology
    Chemical Substances Indoleamine-Pyrrole 2,3,-Dioxygenase ; Interferons (9008-11-1) ; Antiviral Agents
    Language English
    Publishing date 2024-02-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 752392-0
    ISSN 1096-9071 ; 0146-6615
    ISSN (online) 1096-9071
    ISSN 0146-6615
    DOI 10.1002/jmv.29472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice.

    Cai, Jian-Piao / Luo, Cuiting / Wang, Kun / Cao, Hehe / Chen, Lin-Lei / Zhang, Xiaojuan / Han, Yuting / Yin, Feifei / Zhang, Anna Jinxia / Chu, Hin / Yuan, Shuofeng / Kok, Kin-Hang / To, Kelvin Kai-Wang / Chen, Honglin / Chen, Zhiwei / Jin, Dong-Yan / Yuen, Kwok-Yung / Chan, Jasper Fuk-Woo

    Viruses

    2023  Volume 15, Issue 3

    Abstract: The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune ... ...

    Abstract The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion vaccine using wild-type SARS-CoV-2 spike induces a much lower serum neutralizing antibody titre against the Omicron subvariants. Since the inactivated vaccine given intramuscularly is one of the most commonly used coronavirus disease 2019 (COVID-19) vaccines in developing regions, we tested the hypothesis that intranasal boosting after intramuscular priming would provide a broader level of protection. Here, we showed that one or two intranasal boosts with the Fc-linked trimeric spike receptor-binding domain from wild-type SARS-CoV-2 can induce significantly higher serum neutralizing antibodies against wild-type SARS-CoV-2 and the Omicron subvariants, including BA.5.2 and XBB.1, with a lower titre in the bronchoalveolar lavage of vaccinated Balb/c mice than vaccination with four intramuscular doses of inactivated whole virion vaccine. The intranasally vaccinated K18-hACE2-transgenic mice also had a significantly lower nasal turbinate viral load, suggesting a better protection of the upper airway, which is the predilected site of infection by Omicron subvariants. This intramuscular priming and intranasal boosting approach that achieves broader cross-protection against Omicron variants and subvariants may lengthen the interval required for changing the vaccine immunogen from months to years.
    MeSH term(s) Mice ; Animals ; Turbinates ; SARS-CoV-2/genetics ; Viral Load ; COVID-19/prevention & control ; Mice, Transgenic ; Antibodies, Neutralizing ; COVID-19 Vaccines ; Mice, Inbred BALB C ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Antibodies, Neutralizing ; COVID-19 Vaccines ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2023-03-06
    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/v15030687
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A trifunctional peptide broadly inhibits SARS-CoV-2 Delta and Omicron variants in hamsters.

    Zhao, Hanjun / To, Kelvin Kai-Wang / Lam, Hoiyan / Zhang, Chuyuan / Peng, Zheng / Meng, Xinjie / Wang, Xiankun / Zhang, Anna Jinxia / Yan, Bingpeng / Cai, Jianpiao / Yeung, Man Lung / Chan, Jasper Fuk-Woo / Yuen, Kwok-Yung

    Cell discovery

    2022  Volume 8, Issue 1, Page(s) 62

    Abstract: The emergence of highly transmissible SARS-CoV-2 variants has led to the waves of the resurgence of COVID-19 cases. Effective antivirals against variants are required. Here we demonstrate that a human-derived peptide 4H30 has broad antiviral activity ... ...

    Abstract The emergence of highly transmissible SARS-CoV-2 variants has led to the waves of the resurgence of COVID-19 cases. Effective antivirals against variants are required. Here we demonstrate that a human-derived peptide 4H30 has broad antiviral activity against the ancestral virus and four Variants of Concern (VOCs) in vitro. Mechanistically, 4H30 can inhibit three distinct steps of the SARS-CoV-2 life cycle. Specifically, 4H30 blocks viral entry by clustering SARS-CoV-2 virions; prevents membrane fusion by inhibiting endosomal acidification; and inhibits the release of virions by cross-linking SARS-CoV-2 with cellular glycosaminoglycans. In vivo studies show that 4H30 significantly reduces the lung viral titers in hamsters, with a more potent reduction for the Omicron variant than the Delta variant. This is likely because the entry of the Omicron variant mainly relies on the endocytic pathway which is targeted by 4H30. Moreover, 4H30 reduces syncytia formation in infected hamster lungs. These findings provide a proof of concept that a single antiviral can inhibit viral entry, fusion, and release.
    Language English
    Publishing date 2022-06-30
    Publishing country England
    Document type Journal Article
    ISSN 2056-5968
    ISSN 2056-5968
    DOI 10.1038/s41421-022-00428-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters.

    Deng, Shaofeng / Liu, Ying / Tam, Rachel Chun-Yee / Chen, Pin / Zhang, Anna Jinxia / Mok, Bobo Wing-Yee / Long, Teng / Kukic, Anja / Zhou, Runhong / Xu, Haoran / Song, Wenjun / Chan, Jasper Fuk-Woo / To, Kelvin Kai-Wang / Chen, Zhiwei / Yuen, Kwok-Yung / Wang, Pui / Chen, Honglin

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 2081

    Abstract: Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper ... ...

    Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
    MeSH term(s) Animals ; Cricetinae ; Humans ; Influenza Vaccines ; SARS-CoV-2/genetics ; Administration, Intranasal ; COVID-19 Vaccines ; COVID-19/prevention & control ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Neutralizing ; BNT162 Vaccine ; Orthomyxoviridae ; Antibodies, Viral
    Chemical Substances Influenza Vaccines ; spike protein, SARS-CoV-2 ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing ; BNT162 Vaccine ; Antibodies, Viral
    Language English
    Publishing date 2023-04-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-37697-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size

    Carol Ho-Yan Fong / Lu Lu / Lin-Lei Chen / Man-Lung Yeung / Anna Jinxia Zhang / Hanjun Zhao / Kwok-Yung Yuen / Kelvin Kai-Wang To

    iScience, Vol 25, Iss 4, Pp 104037- (2022)

    2022  

    Abstract: Summary: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral ... ...

    Abstract Summary: The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.
    Keywords Biological sciences ; Immunology ; Microbiology ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model.

    Chen, Yanxia / Li, Can / Liu, Feifei / Ye, Zhanhong / Song, Wenchen / Lee, Andrew C Y / Shuai, Huiping / Lu, Lu / To, Kelvin Kai-Wang / Chan, Jasper Fuk-Woo / Zhang, Anna Jinxia / Chu, Hin / Yuen, Kwok-Yung

    Emerging microbes & infections

    2022  Volume 11, Issue 1, Page(s) 368–383

    Abstract: Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely ... ...

    Abstract Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated SARS-CoV-2 pathogenesis, immune responses, and the occurrence of re-infection and vaccine breakthrough infection utilizing a wild-type C57BL/6N mouse model. We demonstrated that interferon and adaptive antibody response upon SARS-CoV-2 challenge are significantly impaired in aged mice compared to young mice, which results in more effective virus replications and severe disease manifestations in the respiratory tract. Aged mice also showed increased susceptibility to re-infection due to insufficient immune protection acquired during the primary infection. Importantly, two-dose COVID-19 mRNA vaccination conferred limited adaptive immune response among the aged mice, making them susceptible to SARS-CoV-2 infection. Collectively, our findings call for tailored and optimized treatments and prevention strategies against SARS-CoV-2 among older individuals.
    MeSH term(s) Age Factors ; Aging/immunology ; Animals ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Disease Models, Animal ; Disease Susceptibility ; Female ; Humans ; Immunity ; Mice ; Mice, Inbred C57BL ; Respiratory System/immunology ; Respiratory System/virology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Vaccination ; Virus Replication
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines
    Language English
    Publishing date 2022-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2022.2026741
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Altered host protease determinants for SARS-CoV-2 Omicron.

    Chan, Jasper Fuk-Woo / Huang, Xiner / Hu, Bingjie / Chai, Yue / Shi, Hongyu / Zhu, Tianrenzheng / Yuen, Terrence Tsz-Tai / Liu, Yuanchen / Liu, Huan / Shi, Jialu / Wen, Lei / Shuai, Huiping / Hou, Yuxin / Yoon, Chaemin / Cai, Jian-Piao / Zhang, Anna Jinxia / Zhou, Jie / Yin, Feifei / Yuan, Shuofeng /
    Zhang, Bao-Zhong / Brindley, Melinda A / Shi, Zheng-Li / Yuen, Kwok-Yung / Chu, Hin

    Science advances

    2023  Volume 9, Issue 3, Page(s) eadd3867

    Abstract: Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the ... ...

    Abstract Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.
    MeSH term(s) Humans ; SARS-CoV-2/metabolism ; Peptide Hydrolases/metabolism ; COVID-19 ; Proteolysis ; Metalloproteases/metabolism ; Virus Internalization
    Chemical Substances Peptide Hydrolases (EC 3.4.-) ; Metalloproteases (EC 3.4.-)
    Language English
    Publishing date 2023-01-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.add3867
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters

    Shaofeng Deng / Ying Liu / Rachel Chun-Yee Tam / Pin Chen / Anna Jinxia Zhang / Bobo Wing-Yee Mok / Teng Long / Anja Kukic / Runhong Zhou / Haoran Xu / Wenjun Song / Jasper Fuk-Woo Chan / Kelvin Kai-Wang To / Zhiwei Chen / Kwok-Yung Yuen / Pui Wang / Honglin Chen

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper ...

    Abstract Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges.

    Lee, Andrew Chak-Yiu / Zhang, Anna Jinxia / Li, Can / Chen, Yanxia / Liu, Feifei / Zhao, Yan / Chu, Hin / Fong, Carol Ho-Yan / Wang, Pui / Lau, Siu-Ying / To, Kelvin Kai-Wang / Chen, Honglin / Yuen, Kwok-Yung

    NPJ vaccines

    2021  Volume 6, Issue 1, Page(s) 95

    Abstract: We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) ... ...

    Abstract We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our results showed that DelNS1-LAIV intradermal vaccination conferred effective and long-lasting protection against lethal virus challenge in mice. A single intradermal injection of DelNS1-LAIV conferred 100% survival with no weight loss in mice after A(H1N1)09 influenza virus (H1N1/415742Md) challenge. DelNS1-LAIV injection resulted in a significant reduction of lung viral load and reduced airway epithelial cell death and lung inflammatory cytokine responses at day 2 and 4 post challenge. Full protections of mice lasted for 6 months after immunization. In vitro infection of DelNS1-LAIV in monocyte-derived dendritic cells (MoDCs) demonstrated activation of antigen-presenting cells at 33 °C, together with the results of abortive replication of DelNS1-LAIV in skin tissue and strong upregulation of inflammatory cytokines/chemokines expression, our results suggested the strong immunogenicity of this vaccine. Further, we demonstrate that the underlying protection mechanism induced by intradermal DelNS1-LAIV is mainly attributed to antibody responses. Together, this study opens up an alternative route for the administration of LAIV, which may benefit individuals not suitable for intranasal LAIV immunization.
    Language English
    Publishing date 2021-08-04
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-021-00359-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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