Intranasal vaccine that induces cellular immunity

Inventors

Yuki, Yoshikazu • NAKAHASHI, Rika • Kiyono, Hiroshi

Assignees

Hanavax Inc • University of Tokyo NUC

Abstract

The present invention provides a nanogel nasal vaccine that induces cell-mediated immunity. The present invention relates to a vaccine preparation comprising a complex of a nanogel, a vaccine antigen, and an adjuvant, wherein the vaccine preparation can efficiently induce the cell-mediated immunity, and can also induce a systemic and mucosal immune response.

Core Innovation

The invention relates to a vaccine preparation comprising a complex of a nanogel, a vaccine antigen, and an adjuvant, where the vaccine antigen is presented together with the nanogel and an adjuvant to induce immune responses. The nanogel is configured to form a complex with the vaccine antigen and adjuvant for administration in a vaccine formulation that targets antigen-specific cellular immunity, and the nanogel adheres to nasal mucosa.

The problem addressed is that prior work showed that nanogel-based mucosal vaccination induced humoral immunity but did not induce cell-mediated immunity, including antigen-specific Th1 and CTL responses. The described rationale is that intranasal delivery using the nanogel complex engages mucosal immunology to produce cellular immune responses rather than only antibody responses, and the invention is therefore directed to inducing antigen-specific Th1 responses and CTL responses after intranasal administration of the nanogel-based vaccine complex.

The described complexes combine a nanogel with a vaccine antigen and an adjuvant, with the adjuvant including one or more STING ligands, including cyclic dinucleotides such as cGAMP and cyclic-di-AMP and cyclic-di-GMP variants. The document reports that this STING-ligand-containing nanogel vaccine complex induces STING-ligand-dependent immune polarization and cellular responses, including Th1/Th17 and CTL/Granzyme B, and is associated with systemic and mucosal immunity after intranasal or transnasal use.

The document further describes specific antigen embodiments for the vaccine antigen portion of the complex, including Mycobacterium tuberculosis antigens such as Ag85B and specified chimeric and gene-product antigens, HPV-derived E6/E7 and especially multiple HPV E7 deletion and mutation variants, and RSV SH peptide. The described results include STING-ligand-dependent Th1/Th17 induction, protection against Mycobacterium tuberculosis in mice with survival and bacterial burden reduction, CTL/Th1 induction in genital mucosa for HPV E7 with STING ligands, and antibody responses including IgG subclasses for RSV SH with cyclic-di-AMP.

Claims Coverage

The independent claim covers a vaccine preparation comprising a complex of a nanogel, a vaccine antigen, and an adjuvant. Across the disclosed claim set, the main inventive features include six overlapping features: nanogel-antigen-adjuvant complex formulation, STING ligand adjuvant, named cyclic dinucleotide STING ligands, Mycobacterium tuberculosis antigens, HPV E7 antigen variants, and transnasal administration for preventing and/or treating infections.

Overall, the claims cover a nanogel-based vaccine preparation in which a complex of a nanogel, a vaccine antigen, and an adjuvant is used, with key refinements specifying STING-ligand adjuvants, selecting vaccine antigens from Mycobacterium tuberculosis gene products or HPV E7 gene product deletion and mutation variants, and further including transnasal administration for preventing and/or treating infections.

Stated Advantages

Documented Applications