Multi-CBV vaccine for preventing or treating type I diabetes

Inventors

Heikki, Hyöty • Knip, Mikael • Laitinen, Olli • Tolonen, Outi • Pulkki, Minna • Oikarinen, Sami • Honkanen, Hanna-Riikka • Lecouturier, Valérie • Almond, Jeffrey • Flodström-Tullberg, Malin

Assignees

Vactech 0y • Vactech Oy

Abstract

The invention is directed to a vaccine comprising: i) coxsackie B virus CBV1 and CBV2, and ii) at least one coxsackie B virus selected from CBV3, CBV4, CBV5 and CBV6. The CBVs are present in the vaccine in inactivated form, in the form of a component of the virus or as an antibody against the virus. The vaccine is effective in preventing and treating type 1 diabetes. So is an anti-coxsackie B virus composition provided.

Core Innovation

The disclosed invention relates to a multi-CBV vaccine/anti-CBV composition for inducing an immune response to coxsackie B virus (CBV) in an individual, for preventing and treating type 1 diabetes. The composition includes CBV1 and CBV2 in inactivated form or in the form of a subunit or a virus-like particle (VLP), together with at least one CBV selected from CBV3, CBV4, and CBV5 in inactivated form or in the form of a subunit or a VLP. The composition excludes CBV6 while still inducing an immune response to CBV in the individual.

The disclosure frames a problem that concerns whether CBV serotypes contribute to type 1 diabetes and how serotypes should be represented to induce protective or beneficial immune effects. It reports rationale that CBVs may be diabetogenic or protective depending on timing/population, and that antibody-mediated cross-reactivity enables broader coverage across CBV serotypes. It also describes that cross-reactivity among CBV serotypes can support coverage beyond the individual included serotypes.

The disclosure provides seroneutralization/statistical evidence and identifies serotype associations in a defined autoantibody seroconversion window. CBV1 is described as a clear risk serotype with strongest association in the 6–0 months before autoantibody seroconversion window, reporting an odds ratio of approximately 3.76 under tight criteria and a population attributable risk of about 58%. CBV2 shows risk trends, and CBV6 is described as gender-dependent risk with a trend in females, supporting selective inclusion/exclusion choices in the multi-CBV composition.

The disclosure also provides preclinical support linking CBV1 and immune outcomes to type 1 diabetes–relevant effects and to antiviral/antiprotection measures. It reports that an inactivated CBV1 vaccine induces neutralizing antibodies and protects mice from viremia/pancreatic infection, and that CBV1 can trigger diabetes in SOCS-1 transgenic NOD mice. Further, it reports antibody cross-reactivity among CBV serotypes and sequencing data showing CBV predominance in T1D case children, supporting a causal role for CBVs.

Claims Coverage

The independent claim covers a method of inducing an immune response to coxsackie B virus (CBV) by administering a defined multi-serotype composition containing CBV1 and CBV2 plus at least one of CBV3, CBV4, and CBV5, while excluding CBV6. The independent claim includes multiple inventive features, including the specified CBV serotype set and the antigen presentation formats.

Overall, the claim coverage focuses on inducing an immune response to CBV using a multi-serotype composition defined by CBV1 and CBV2 plus at least one of CBV3, CBV4, or CBV5, presented as inactivated, subunits, or VLPs, and explicitly excluding CBV6.

Stated Advantages

Documented Applications