Methods of enhancing immunogenicity of poorly immunogenic antigen-specific vaccines using oral yeast beta-glucans

Inventors

Cheung, Nai-Kong • MODAK, Shakeel • Ragupathi, Govind

Assignees

Memorial Sloan Kettering Cancer Center

Abstract

The present disclosure provides methods for enhancing the immunogenicity of a poorly immunogenic antigen-specific vaccine as well as methods for promoting diversification of the gut microbiome in a subject in need thereof comprising administering to the subject an effective amount of a beta-glucan extract derived from yeast. Kits for use in practicing the methods are also provided.

Core Innovation

The disclosure describes methods and kits for enhancing immunogenicity of a poorly immunogenic antigen-specific vaccine by administering, to a subject in need thereof, an effective amount of the poorly immunogenic antigen-specific vaccine together with an orally administered yeast-derived soluble beta-glucan. The poorly immunogenic antigen-specific vaccine comprises at least one poorly immunogenic antigen that is optionally linked to a carrier, and the vaccine is not a whole cell tumor vaccine.

The yeast beta-glucan comprises a plurality of β-(1,3) side chains linked to a β-(1,3) backbone via β-(1,6) linkages, and has a range of average molecular weights from about 6 kDa to about 30 kDa. Administration of the poorly immunogenic antigen-specific vaccine and the yeast beta-glucan induces at least a 1.5-fold increase in therapeutic IgG antibody titer levels in the subject compared to a control subject that receives the poorly immunogenic antigen-specific vaccine without the yeast beta-glucan.

The disclosure further describes that the enhanced immunologic outcomes include increases in therapeutic antibody titers and persistence of titers. In addition, the disclosure reports that oral yeast beta-glucan increases gut microbiome diversity in dysbiosis and chemotherapy-exposed subjects, and provides supporting preclinical and clinical evidence, including Phase I/II neuroblastoma trials using anti-GD2 and anti-GD3 titers.

Claims Coverage

The partial claim set provided identifies one independent claim. It requires two-part administration: a poorly immunogenic antigen-specific vaccine, not a whole cell tumor vaccine, and a structurally defined yeast beta-glucan with specified backbone/side-chain architecture and molecular weight range, together producing at least a 1.5-fold increase in therapeutic IgG antibody titers versus a control without the yeast beta-glucan.

Across the provided independent claim, the inventive concept centers on inducing a therapeutic IgG antibody titer increase by co-administering a not-whole-cell poorly immunogenic antigen-specific vaccine with a structurally defined yeast beta-glucan, achieving at least a 1.5-fold increase versus control.

Stated Advantages

Documented Applications