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Publication Number

US-11850280-B1

Patent

Publication Date

2023-12-26

Expiration Date


Abstract

The inventive subject matter includes a viral-vectored composition made of a bacterial expression vehicle expressing one or more recombinant viral protein antigens and its method of use. In particular, this invention relates to a vaccine for oral administration. Preferably, the bacterial expression vehicle is Bacillus subtilis.

Core Innovation

The invention relates to an oral vaccine for Peste-des-Petits-Ruminants virus (PPRV) that uses a Bacillus subtilis bacterial antigen expression vehicle engineered to express recombinant viral protein antigens. The recombinant antigen is a PPRV hemagglutinin protein (PPRV-H), and the concept is described in relation to mucosal immunological response targeting. The approach is positioned to address limitations of current PPR vaccination, including cold chain and injection logistics, as well as lack of DIVA.

The oral administration concept is implemented using a coated solid substrate and a layered, stabilized vaccine matrix. The PPRV-H is stabilized within a liquid carrier matrix, and then the stabilized hemagglutinin is coated onto a solid support. Surface encapsulation is achieved by adding a cross-linking agent, with hydrocolloids such as sodium alginate and calcium-based encapsulation described as stabilization and encapsulation mechanisms.

The document further describes that the coating/encapsulation substrate can involve ruminant undegradable protein (RUP) and optional enteric coating, and that the design aims to support rumen bypass and gastrointestinal dissolution. Mucosal immune targeting is described through GALT/MALT, and proof-of-concept immune responses are presented in a goat model with serum antibody responses to GFP and PPRV-H.

Claims Coverage

The partial content includes three independent claims, each directed to an oral vaccine composition using Bacillus subtilis expressing PPRV hemagglutinin, an oral vaccine coated solid support produced by a stabilization/coating/encapsulation process, and a vaccine antigen expression system using a Bacillus subtilis antigen expression vehicle to express one or more recombinant PPRV viral protein antigens engineered from hemagglutinin and including a vaccine carrier substrate. The main inventive features are captured by these three independent claims.

Oral vaccine with Bacillus subtilis expressing PPRV hemagglutinin

An oral vaccine comprising an expression vehicle including Bacillus subtilis expressing a hemagglutinin protein from Peste-des-Petits-Ruminants virus (PPRV).

Coated solid support vaccine with stabilized PPRV hemagglutinin and cross-linking encapsulation

A vaccine coated solid support made by a process that stabilizes PPRV hemagglutinin within a liquid carrier matrix, coats the stabilized PPRV hemagglutinin onto a solid support, and encapsulates the PPRV hemagglutinin on the surface of the solid support by adding a cross-linking agent.

Vaccine antigen expression system with Bacillus subtilis expressing recombinant viral protein antigens from PPRV hemagglutinin

A vaccine antigen expression system including a bacterial antigen expression vehicle comprising Bacillus subtilis configured to express one or more recombinant viral protein antigens, where the one or more recombinant viral protein antigens are engineered from a hemagglutinin protein from Peste-des-Petits-Ruminants virus (PPRV) and a vaccine carrier substrate.

Across the independent claims, the inventive subject matter centers on oral vaccination using a Bacillus subtilis expression vehicle for PPRV hemagglutinin, combined with a coated solid support approach in which the hemagglutinin is stabilized in a liquid carrier matrix and surface-encapsulated using a cross-linking agent, and on an antigen expression system where recombinant viral protein antigens are engineered from PPRV hemagglutinin and a vaccine carrier substrate.

Stated Advantages

Addresses cold chain and injection logistics limitations of current PPR vaccination.

Addresses lack of DIVA in current PPR vaccination.

Provides targeting of mucosal immunological response via GALT/MALT.

Documented Applications

Oral administration of a PPRV vaccine using a Bacillus subtilis expression vehicle expressing PPRV hemagglutinin (PPRV-H).

Ruminant/goat proof-of-concept immune response evaluation, including serum IgG responses to GFP and PPRV-H.

Mucosal immunological response targeting via GALT/MALT in the context of an oral PPRV vaccination concept.

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