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NF-KB Inhibitors As Immune Potentiators For Increased Safety And Improved Protection Of Vaccines

Inventor(s):

Technology Classifications > Therapeutics

    SUMMARY

    • The development of vaccines against challenging targets such as Dengue and HIV is limited in part by a lack of suitable adjuvants. TLR agonists such as CpG have been shown in the clinic to be sufficiently immune-activating for these targets, but they often promote excess inflammation.
    • It is known that transcription factor NF-KB controls both inflammatory expression and antigen presentation. The inventors discovered a panel of immune-modulating agents that selectively enhance antigen presentation and adaptive immune responses, while decreasing inflammation.
    • The invention includes peptide (SN50) and small molecule NF-KB inhibitors that selectively and locally limit inflammation and potentiate the protective response of adjuvants. Combination with common immune adjuvants allows for the use of new vaccine formulations that would otherwise promote aggressive inflammatory responses.
    • In proof-of-concept experiments using SN50, influenza (Fluzone 2017/2018 tetravalent), dengue (DENV-2C capsid), and HIV (GP120) vaccines were evaluated with a CpG adjuvant. Results showed that SN50 decreases pro-inflammatory cytokines without impacting IgG titers, T cell response, or vaccine protection. Select small molecule inhibitors were tested in an ovalbumin (OVA) model with a CpG adjuvant, and they were shown to decrease the production of pro-inflammatory cytokines while boosting antibody levels.

    FIGURE

    Influenza proof of concept data with Fluzone. Mice were injected intramuscularly with different combinations of the Fluzone vaccine (Fz), CpG vaccine adjuvant (CpG), high and low doses of the SN50 peptide additive (SN50 H, SN50 L). Mice were boosted on day 21. A-B show cytokine levels at injection site 1 hour post injection (N=13). C shows IgG levels 28 days after injection (N=13). D shows mice survival in response to challenge, day 0 is 43 days after initial injection and 15 days after boost (N=5).

    ADVANTAGES

    ADVANTAGES

    • Reduces inflammatory response of vaccine adjuvants
    • Does not impact adaptive immune responses
    • Mechanism of action is local to injection site
    • Applicable to a broad range of vaccine formulations

    APPLICATIONS

    • Adjuvant additive in both recombinant and whole virus vaccines
    • Platform technology with multi-target applicability including influenza, dengue, and HIV

    PUBLICATIONS

    TECH DETAILS

    Published
    6/17/2020

    Reference ID
    18-T-658

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