Live attenuated chimeric porcine circovirus vaccine

Inventors

Meng, Xiang-JinBEACH, NATHAN M.RAMAMOORTHY, SHEELA

Assignees

Virginia Tech Intellectual Properties IncVirginia Polytechnic Institute and State University

Publication Number

US-9585951-B2

Publication Date

2017-03-07

Expiration Date

2031-03-16

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Abstract

The present invention provides a novel chimeric porcine circovirus infectious DNA clone and live attenuated chimeric virus with the PCV2, preferably of subtype PCV2b, capsid gene integrated into a non-pathogenic PCV1 virus genome. In a particular embodiment, the PCV2 capids gene is of subtype PCV2b, the predominant subtype circulating in pigs worldwide. The attenuated chimeric virus, designated PCV1-2b, effectively protects pigs from PCV2b challenges, and can be used as a live vaccine, as well as an inactivated (killed) vaccine, that provides protection and cross protection against PCV2b and PCV2a subtypes infection. The live attenuated vaccine of the present invention is also effective protecting pigs from porcine circovirus-associated disease (PCVAD).

Core Innovation

The invention provides a novel chimeric porcine circovirus (PCV) infectious DNA clone and live attenuated chimeric virus, in which the capsid gene of PCV2, preferably the PCV2b subtype, is integrated into the non-pathogenic PCV1 virus genome. The resulting attenuated chimeric virus, designated PCV1-2b, is designed to be used as either a live vaccine or an inactivated (killed) vaccine, offering protection and cross protection against both PCV2b and PCV2a subtypes of PCV infection.

The problem addressed by this invention stems from the global emergence of PCV2b, a pathogenic subtype responsible for severe porcine circovirus-associated disease (PCVAD), and concerns regarding whether existing vaccines based on the PCV2a genotype offer adequate protection against PCV2b. Current commercial vaccines are all killed or recombinant and predominantly based on PCV2a; with the predominance of PCV2b and the increased severity of PCVAD, there is a need for a PCV2b-based vaccine, ideally as a live attenuated version to provide enhanced protection.

This invention achieves attenuation by constructing a virus that combines the non-pathogenic PCV1 backbone with the immunogenic capsid gene from the PCV2b subtype, resulting in a chimeric viral genome. The constructed PCV1-2b virus has been shown to be attenuated in animal models but induces a strong immune response and provides protection against clinical disease and lesion development upon challenge with both PCV2b and PCV2a wildtype viruses.

Claims Coverage

The patent includes four independent claims, which together cover the core inventive features involving a chimeric PCV1-2b virus, its structure and genetic makeup, related viral vaccines, and specific methods of immunizing and protecting pigs using these vaccines.

Chimeric PCV1-2b virus with PCV2b capsid gene in place of PCV1 capsid

A chimeric PCV1-2b virus comprising a recombinant PCV1 that encodes the capsid protein of PCV2b subtype in place of the capsid protein of PCV1. The capsid protein of the PCV2b subtype is encoded by the ORF2 capsid gene of a wild-type PCV2b strain having the full-length genomic nucleotide sequence set forth in SEQ ID NO: 2.

Viral vaccine containing immunogenic amount of chimeric PCV1-2b virus

A viral vaccine comprising a physiologically acceptable carrier and an immunogenic amount of the chimeric PCV1-2b virus as defined above, with the capsid protein of the PCV2b subtype encoded by the ORF2 capsid gene of a wild-type PCV2b strain having SEQ ID NO: 2.

Method of immunizing a pig against PCV2 using the chimeric PCV1-2b vaccine

A method of immunizing a pig against PCV2 viral infection by administering an immunologically effective amount of the above-defined vaccine.

Method of protecting a pig against porcine circovirus-associated disease (PCVAD) using the chimeric PCV1-2b vaccine

A method of protecting a pig against porcine circovirus-associated disease (PCVAD) by administering an immunologically effective amount of the vaccine composed of a chimeric PCV1-2b virus defined as above.

The patent claims cover the composition and specific genetic configuration of a chimeric PCV1-2b virus, its formulation into immunogenic vaccines, and methods of using these vaccines for immunization and protection of pigs against PCV2 infection and PCVAD.

Stated Advantages

The live attenuated chimeric virus is genetically stable, easier to make, store, and deliver than other types of attenuated vaccines.

The invention provides an attenuated, live vaccine that avoids the risk of reversion to virulence or insufficient immune response associated with traditional live or killed vaccines.

The vaccine induces strong humoral immune response and provides both protective and cross-protective immunity against PCV2a and PCV2b subtypes, and reduces microscopic lesions, viremia, and antigen presence in tissues.

Live vaccines activate all possible immune responses in the vaccine recipient, including systemic, local, humoral, and cell-mediated immune responses.

Documented Applications

Immunization of pigs against PCV2 viral infection using the chimeric PCV1-2b vaccine.

Protection of pigs against porcine circovirus-associated disease (PCVAD) by administration of the chimeric PCV1-2b vaccine.

Use as a live attenuated or inactivated vaccine to provide protection and cross protection against PCV2b and PCV2a subtypes infection.

Potential use in combination with current PCV2a-based commercial vaccines for broader protection.

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