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  1. Article ; Online: Single-cell suspension preparation from murine organs following in vivo mRNA-LNP exposure

    Sonia Ndeupen / Zhen Qin / Botond Z. Igyártó

    STAR Protocols, Vol 3, Iss 2, Pp 101350- (2022)

    2022  

    Abstract: Summary: We describe a protocol to study inflammatory responses triggered by the mRNA-lipid nanoparticle (LNP) vaccine formulations in skin, muscle, and lung and the adaptive immune responses induced in the draining lymph nodes. Here, we will present how ...

    Abstract Summary: We describe a protocol to study inflammatory responses triggered by the mRNA-lipid nanoparticle (LNP) vaccine formulations in skin, muscle, and lung and the adaptive immune responses induced in the draining lymph nodes. Here, we will present how to deliver these reagents through intradermal, intramuscular, and intranasal routes, generating single-cell suspensions from the inoculated and target organs for downstream analyses.For complete details on the use and execution of this protocol, please refer to Ndeupen et al. (2021) and (2022).
    Keywords Health Sciences ; Immunology ; Science (General) ; Q1-390
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

    Sonia Ndeupen / Zhen Qin / Sonya Jacobsen / Aurélie Bouteau / Henri Estanbouli / Botond Z. Igyártó

    iScience, Vol 24, Iss 12, Pp 103479- (2021)

    2021  

    Abstract: Summary: Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. ...

    Abstract Summary: Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against COVID-19. Clinical trials and ongoing vaccinations present with varying degrees of protection levels and side effects. However, the drivers of the reported side effects remain poorly defined. Here we present evidence that Acuitas' LNPs used in preclinical nucleoside-modified mRNA vaccine studies are highly inflammatory in mice. Intradermal and intramuscular injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate, with mechanism unresolved. Thus, the mRNA-LNP platforms' potency in supporting the induction of adaptive immune responses and the observed side effects may stem from the LNPs' highly inflammatory nature.
    Keywords Biological sciences ; Immunology ; Biotechnology ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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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.

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

    PLoS Pathogens, Vol 18, Iss 1, p e

    2022  Volume 1010255

    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.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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