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    Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge.

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    Author
    Wong, Ting Y
    Lee, Katherine S
    Russ, Brynnan P
    Horspool, Alexander M
    Kang, Jason
    Winters, Michael T
    Allison Wolf, M
    Rader, Nathaniel A
    Miller, Olivia A
    Shiflett, Morgane
    Izac, Jerilyn
    Varisco, David
    Sen-Kilic, Emel
    Cunningham, Casey
    Cooper, Melissa
    Cyphert, Holly A
    Barbier, Mariette
    Martinez, Ivan
    Bevere, Justin R
    Ernst, Robert K
    Damron, F Heath
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    Date
    2022-03-14
    Journal
    NPJ Vaccines
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1038/s41541-022-00451-7
    Abstract
    SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM®). The vaccine is adjuvanted with Bacterial Enzymatic Combinatorial Chemistry (BECC), BECC470. Intranasal (IN) administration of BreC-CoV-2 in K18-hACE2 mice induced a strong systemic and localized immune response in the respiratory tissues which provided protection against the Washington strain of SARS-CoV-2. Protection provided after IN administration of BReC-CoV-2 was associated with decreased viral RNA copies in the lung, robust RBD IgA titers in the lung and nasal wash, and induction of broadly neutralizing antibodies in the serum. We also observed that BReC-CoV-2 vaccination administered using an intramuscular (IM) prime and IN boost protected mice from a lethal challenge dose of the Delta variant of SARS-CoV-2. IN administration of BReC-CoV-2 provided better protection than IM only administration to mice against lethal challenge dose of SARS-CoV-2. These data suggest that the IN route of vaccination induces localized immune responses that can better protect against SARS-CoV-2 than the IM route in the upper respiratory tract.
    Rights/Terms
    © 2022. The Author(s).
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18343
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41541-022-00451-7
    Scopus Count
    Collections
    UMB Coronavirus Publications
    UMB Open Access Articles

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