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  1. Article ; Online: Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract.

    Kurup, Drishya / Wirblich, Christoph / Lambert, Rachael / Diba, Leila Zabihi / Leiby, Benjamin E / Schnell, Matthias J

    NPJ vaccines

    2022  Volume 7, Issue 1, Page(s) 43

    Abstract: Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV- ... ...

    Abstract Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested MV-based vaccines that expressed E and NS1 together or separately in two different vaccines. We observed complete clearance of ZIKV from the female reproductive tract and complete fetal protection in the lethal African challenge model in animals that received the dual antigen vaccines. Additionally, MV-E2 and MV-NS1, when administered together, induced durable plasma cell responses. Our findings suggest that NS1 antibodies are required to enhance the protection of ZIKV-E antibodies in the female reproductive tract.
    Language English
    Publishing date 2022-04-19
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-022-00464-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses.

    Ndeupen, Sonia / Bouteau, Aurélie / Herbst, Christopher / Qin, Zhen / Hutchins, Zachary / Kurup, Drishya / Diba, Leila Zabihi / Igyártó, Botond Z

    bioRxiv : the preprint server for biology

    2021  

    Abstract: Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently ... ...

    Abstract Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs' ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses. In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.
    Language English
    Publishing date 2021-08-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.08.01.454662
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses.

    Ndeupen, Sonia / Bouteau, Aurélie / Herbst, Christopher / Qin, Zhen / Jacobsen, Sonya / Powers, Nicholas E / Hutchins, Zachary / Kurup, Drishya / Diba, Leila Zabihi / Watson, Megan / Ramage, Holly / Igyártó, Botond Z

    PLoS pathogens

    2022  Volume 18, Issue 1, Page(s) e1010255

    Abstract: Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently ... ...

    Abstract Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs' ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge. In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines.
    MeSH term(s) Animals ; COVID-19/immunology ; COVID-19 Vaccines/immunology ; Dendritic Cells/immunology ; Influenza Vaccines/immunology ; Langerhans Cells/immunology ; Liposomes/immunology ; Mice ; Nanoparticles ; Orthomyxoviridae Infections/immunology ; SARS-CoV-2/immunology ; Vaccines, Synthetic/immunology ; mRNA Vaccines/immunology
    Chemical Substances COVID-19 Vaccines ; Influenza Vaccines ; Lipid Nanoparticles ; Liposomes ; Vaccines, Synthetic ; mRNA Vaccines
    Language English
    Publishing date 2022-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010255
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses

    Ndeupen, Sonia / Bouteau, Aurelie / Herbst, Christopher / Qin, Zhen / Hutchins, Zachary / Kurup, Drishya / Diba, Leila Zabihi / Igyarto, Botond

    bioRxiv

    Abstract: Nucleoside modified mRNA combined with Acuitas Therapeutics9 lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently ... ...

    Abstract Nucleoside modified mRNA combined with Acuitas Therapeutics9 lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs9 ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses. In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.
    Keywords covid19
    Language English
    Publishing date 2021-08-02
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.08.01.454662
    Database COVID19

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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