Viable viruses with foreign tags

Inventors

Faaberg, Kay S.Spear, AllynKappes, Matthew A.Lager, Kelly M.

Assignees

US Department of Agriculture USDA

Publication Number

US-10729756-B2

Publication Date

2020-08-04

Expiration Date

2038-05-25

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Abstract

Multiple DIVA vaccines effective against porcine reproductive and respiratory syndrome virus (PRRSV) are disclosed. The DIVA vaccines may be negative DIVAs or positive DIVAs. The DIVA vaccines may be produced by modifying the nsp2 region of a modified live virus vaccine. The modification may be one or more deletions only (negative DIVAs) or a deletion with an insertion (positive DIVAs). The insertion may be of an epitope tag, such as a V5, S-Tag, or FLAG tag. Produced DIVA vaccines may be stable through multiple passes and thus may be effective for production and vaccination of animals.

Core Innovation

The invention discloses multiple DIVA vaccines effective against porcine reproductive and respiratory syndrome virus (PRRSV). These DIVA vaccines may be either negative DIVAs, involving one or more deletions only, or positive DIVAs, involving a deletion with an insertion such as an epitope tag (e.g., V5, S-Tag, or FLAG). The vaccines are produced by modifying the nsp2 region of a modified live virus vaccine, and the produced DIVA vaccines are stable through multiple passages, enabling effective production and vaccination.

The problem being solved is the lack of a vaccine for PRRSV that effectively differentiates infected from vaccinated animals (DIVA) and provides broad protection against the highly variable and evolving PRRSV strains. Current modified live vaccines provide only partial protection against heterologous viruses and do not allow differentiation between infected and vaccinated animals, which impedes disease control in the swine industry.

Claims Coverage

The patent includes three independent claims covering immunogenic compositions with modified nsp2 regions of PRRSV vaccines and a method of reducing PRRSV incidence by administering such vaccines. The inventive features focus on the specific modifications of the nsp2 amino acid sequences and the vaccine composition components.

Modified nsp2 region inclusion in immunogenic composition

An immunogenic composition comprising an isolated polynucleotide representing a modified live vaccine for PRRSV with an nsp2 region having an amino acid sequence of specific variants (SEQ ID NOs: 3, 13, 15, 17 or with at least 99% homology) and including a pharmaceutically acceptable adjuvant, capable of inducing an immune response.

Inclusion of pharmaceutically acceptable carrier in immunogenic composition

The immunogenic composition further includes a pharmaceutically acceptable carrier along with the modified live vaccine polynucleotide and adjuvant.

Alternative nsp2 region variants in immunogenic composition

An immunogenic composition comprising an isolated polynucleotide representing a modified live vaccine for PRRSV with nsp2 region amino acid sequences selected from SEQ ID NOs: 5, 19, 21, 23, or sequences having at least 99% homology, with a pharmaceutically acceptable adjuvant, capable of eliciting an immune response.

Method for reducing PRRSV incidence in swine using modified nsp2 vaccines

A method comprising administering to swine an immunogenic composition with an isolated polynucleotide representing a modified live vaccine for PRRSV having an nsp2 region with the specific amino acid sequences (as in the immunogenic compositions), in an amount effective to induce protective immune response against PRRSV infection.

The claims collectively cover vaccine compositions incorporating specific modified nsp2 region sequences with deletions and optional insertions (epitope tags), optionally including carriers and adjuvants, and methods of using such vaccine compositions for protection against PRRSV in swine.

Stated Advantages

The produced DIVA vaccines are stable through multiple passages, thus suitable for production and vaccination of animals.

Vaccines enable differentiation between infected and vaccinated animals (DIVA), aiding disease management and control.

The vaccines replicate sufficiently in vaccinated swine with reduced risk of reversion to virulence and provide protection without causing severe disease symptoms.

Documented Applications

Vaccination of swine to reduce incidence and provide protection against porcine reproductive and respiratory syndrome virus (PRRSV) infection.

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