Mosaic vaccines for serotype a foot-and-mouth disease virus
Inventors
Rieder, Aida E. • Fischer, William M. • RAI, DEVENDRA K.
Assignees
US Department of Agriculture USDA • Triad National Security LLC
Publication Number
US-10172933-B2
Publication Date
2019-01-08
Expiration Date
2037-10-17
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Abstract
Synthetic foot-and-mouth disease virus (FMDV) mosaic polypeptides, and nucleic acid molecules encoding the mosaic polypeptides, are described. The mosaic polypeptides have greater T-cell epitope coverage than naturally occurring FMDV polypeptides, and include common FMDV epitopes, but exclude rare FMDV epitopes. When included as part of an FMDV genome, the mosaic polypeptides permit virus replication and assembly into FMDV particles. The mosaic polypeptide and nucleic acid compositions can be used to elicit immune responses that provide protection against a broad range of serotype A FMDV strains.
Core Innovation
The invention relates to synthetic foot-and-mouth disease virus (FMDV) mosaic polypeptides and nucleic acid molecules encoding these polypeptides, designed to provide greater T-cell epitope coverage than naturally occurring FMDV polypeptides. These mosaic polypeptides include common FMDV epitopes but exclude rare ones, and when incorporated into an FMDV genome, they permit virus replication and assembly into particles that elicit broader immune responses against serotype A FMDV strains.
The problem addressed is the economic and health challenge posed by FMDV, a highly infectious virus affecting livestock with seven major serotypes and high within-serotype diversity, which limits cross-protection by current vaccines that target inactivated virus. Existing vaccines have unsatisfactory cost, safety, duration of immunity, and limited breadth of protection, necessitating large stockpiles to cover outbreak diversity. Thus, there is a need to improve the breadth of vaccine-induced protection across different FMDV strains.
The invention applies the mosaic design method, previously used for HIV-1 vaccines, to FMDV to optimize synthetic viral protein sequences, maximizing the number of potential epitopes weighted by population frequency. The resulting synthetic mosaic polypeptides have higher T-cell epitope coverage compared to natural sequences, limiting inclusion of rare or unnatural epitopes. These polypeptides enable replication and structure formation of infectious virus similar to native FMDV, facilitating production of vaccine compositions that elicit protective immune responses against diverse serotype A strains.
Claims Coverage
This patent includes multiple independent claims covering synthetic polypeptides, recombinant viruses, nucleic acid molecules, vectors, compositions, and methods for eliciting immune responses based on FMDV mosaic polypeptides.
Synthetic polypeptides with high sequence identity to mosaic FMDV capsid proteins
The synthetic polypeptides comprise amino acid sequences at least 98% identical to either SEQ ID NO: 2 or SEQ ID NO: 4, corresponding to mosaic FMDV capsid proteins VP4.2.1 or VP4.2.2.
Recombinant foot-and-mouth disease viruses comprising mosaic polypeptides
Recombinant FMDV includes synthetic polypeptides at least 98% identical to SEQ ID NO: 2 or SEQ ID NO: 4, enabling viral replication and assembly with mosaic capsid sequences.
Nucleic acid molecules encoding mosaic FMDV polypeptides and vectors
Isolated nucleic acid molecules encoding synthetic polypeptides at least 98% identical to SEQ ID NO: 2 or SEQ ID NO: 4, and vectors comprising these nucleic acids. Certain vectors include coding sequences for FMDV L, VP4, P2, and P3 proteins, permitting production of infectious FMDV upon transfection.
Compositions comprising mosaic polypeptides or recombinant viruses
Compositions containing synthetic polypeptides or recombinant FMDVs with mosaic capsid proteins, pharmaceutically acceptable carriers, and optionally adjuvants are provided.
Methods of eliciting immune responses against serotype A FMDV
Methods involve administering to a subject a composition comprising synthetic polypeptides at least 98% identical to SEQ ID NO: 2 or SEQ ID NO: 4, alone or as a bivalent vaccine with two compositions administered at different anatomical sites, to elicit protective immune responses against serotype A FMDV.
The independent claims collectively define synthetic mosaic polypeptides closely matching disclosed sequences, recombinant viruses carrying these polypeptides, nucleic acid encodings and vectors, compositions suitable for vaccination, and methods of immunization targeting broad serotype A FMDV protection using bivalent mosaic vaccine components.
Stated Advantages
The mosaic FMDV polypeptides provide higher T-cell epitope coverage than natural or consensus FMDV sequences, enhancing immune response breadth.
They exclude rare or unnatural epitopes, optimizing vaccine efficacy and safety.
Recombinant viruses incorporating mosaic polypeptides replicate and assemble into native-like viral particles, facilitating vaccine production.
The vaccine compositions elicit protection against a broad range of serotype A FMDV strains, reducing the need for multiple strain-specific vaccines.
Demonstrated efficacy in cattle against diverse serotype A FMDV challenge strains, showing high protection rates and prevention of clinical disease and viremia.
Documented Applications
Use of synthetic mosaic FMDV polypeptides, nucleic acid molecules, vectors, recombinant viruses, and compositions as vaccines to elicit immune responses and protect cloven-hoofed animals, especially cattle, against serotype A foot-and-mouth disease virus infection.
Administration of bivalent vaccine compositions containing two distinct mosaic polypeptides to animals to provide broad protection against diverse serotype A FMDV strains.
Production of recombinant infectious FMDV incorporating mosaic capsid proteins for vaccine development and immunization purposes.
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