Immunogenic composition and uses thereof
Inventors
Jackson, David Charles • Zeng, Weiguang • Chua, Brendon Yew Loong
Assignees
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Publication Number
US-9889195-B2
Publication Date
2018-02-13
Expiration Date
Abstract
The present invention provides an immunogenic composition comprising an antigen and a dendritic cell targeting component. A charged group is covalently attached to a dendritic cell ligand and is electrostatically associated with the dendritic cell targeting component.
Core Innovation
The invention relates to an immunogenic composition that comprises a complex of a polypeptide antigen and a dendritic cell targeting component. The polypeptide antigen comprises a negatively charged region, and the negatively charged region electrostatically associates with the dendritic cell targeting component to enable formation of the complex.
The dendritic cell targeting component is configured for dendritic cell targeting and includes a charged group covalently attached to a dendritic cell ligand. Dendritic cell ligand targeting uses Pam2Cys, which refers to dipalmitoyl-S-glycerylcysteine and is associated with Toll-like receptor 2 (TLR-2).
The disclosure describes charged lipopeptide constructs, including branched and linear forms such as R4(S2Pam2Cys) and E4(S2Pam2Cys). The complexes are formed through electrostatic association, with the antigen described as not a nucleic acid, and the disclosure reports binding and complex formation supported by turbidity, sedimentation, and HPLC analyses.
Claims Coverage
The independent claim covers an immunogenic composition based on a charge-governed complex between a polypeptide antigen and a dendritic cell targeting component, with Pam2Cys explicitly defined. Dependent claims add constraints regarding overall charge and restricting the association mechanism to electrostatic interaction only.
Charge-based antigen–dendritic cell targeting complex
An immunogenic composition comprising a complex of a polypeptide antigen and a dendritic cell targeting component, wherein the polypeptide antigen comprises a negatively charged region, wherein the negatively charged region of the polypeptide antigen electrostatically associates with the dendritic cell targeting component, thereby enabling formation of the complex.
Pam2Cys definition for dendritic cell ligand targeting
The dendritic cell targeting component wherein Pam2Cys refers to dipalmitoyl-S-glycerylcysteine.
Overall negative charge constraint
The polypeptide antigen has an overall negative charge.
Electrostatic association only
The polypeptide antigen is associated with the dendritic cell targeting component by electrostatic interaction only.
Overall, the claim set focuses on forming an immunogenic complex through electrostatic association of a polypeptide antigen containing a negatively charged region with a dendritic cell targeting component, with Pam2Cys explicitly defined and additional constraints requiring overall negative charge and electrostatic-only association.
Stated Advantages
Increases antigen-specific antibody and/or CD8+ IFN-γ responses.
Enables binding and complex formation, supported by turbidity, sedimentation, and HPLC analyses.
Allows ratio-dependent tuning of humoral versus cellular responses.
Documented Applications
Raising immune responses including antigen-specific antibody responses and/or CD8+ IFN-γ responses in mice.
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