BACTERIOPHAGE-BASED, NEEDLE AND ADJUVANT-FREE, MUCOSAL COVID-19 VACCINE

    公开(公告)号:US20230355738A1

    公开(公告)日:2023-11-09

    申请号:US18138183

    申请日:2023-04-24

    CPC classification number: A61K39/12 A61P37/04 A61K2039/545

    Abstract: A bacteriophage T4-based, multivalent/multicomponent, needle and adjuvant-free, mucosal vaccine by engineering spike trimers on capsid exterior and nucleocapsid protein in the interior is disclosed herein. Intranasal administration of this T4-COVID vaccine induces higher virus neutralization antibody titers against multiple variants, balanced Th1/Th2 antibody and cytokine responses, stronger CD4+ and CD8+ T cell immunity, and higher secretory IgA titers in sera and bronchoalveolar lavage with no effect on the gut microbiota, compared to vaccination of mice intramuscularly. The vaccine is stable at ambient temperature, induce apparent sterilizing immunity, and provide complete protection against original SARS-CoV-2 strain and its Delta variant with minimal lung histopathology. This mucosal vaccine is an excellent candidate for boosting immunity of immunized and/or as a second-generation vaccine for the unimmunized population. This needle-free platform could be used to develop effective vaccines against many other respiratory infectious pathogens including Flu and any future emerging epidemic and pandemic pathogens.

    ENGINEERING OF BACTERIOPHAGES BY GENOME EDITING USING THE CRISPR-CAS9 SYSTEM

    公开(公告)号:US20190330643A1

    公开(公告)日:2019-10-31

    申请号:US16355932

    申请日:2019-03-18

    Abstract: Embodiments of the invention provide systems, methods, and kits for CRISPR-based editing of DNA targets by a CRISPR-associated (Cas) enzyme. The systems include a bacterial host cell adapted to produce an engineered bacteriophage comprising a Cas protein and guide RNA that do not naturally occur together, i.e. they are engineered to occur together, as well as a DNA repair template comprising a donor DNA having a desired mutation. The guide RNA comprises a trans-activating crRNA and a guide sequence complementary to a target protospacer in a bacteriophage genome. A wild-type bacteriophage or a glucosylhydroxymethyl cytosine (ghmC)-unmodified mutant bacteriophage may be delivered into a disclosed bacterial host cell to create recombinants of bacteriophage having the desired mutation provided by the donor DNA.

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