Live attenuated chimeric porcine circovirus vaccine
Inventors
Meng, Xiang-Jin • BEACH, NATHAN M. • RAMAMOORTHY, SHEELA
Assignees
Virginia Tech Intellectual Properties Inc • Virginia Polytechnic Institute and State University
Publication Number
US-9610344-B2
Publication Date
2017-04-04
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, wherein the capsid gene of PCV2, preferably of subtype PCV2b, is integrated into a non-pathogenic PCV1 virus genome. This genetic construction creates an attenuated chimeric virus, designated PCV1-2b, which effectively induces immunity against PCV2b and can be utilized as both a live vaccine and an inactivated vaccine for protection against PCV2a and PCV2b infections.
The problem addressed arises from the global shift in the prevalence of PCV2b subtype, now the predominant and more pathogenic agent causing porcine circovirus-associated disease (PCVAD) in pig populations worldwide. Existing commercial vaccines are primarily based on the PCV2a subtype, raising concerns about their efficacy against the emerging PCV2b subtype and the rising severity of PCVAD. The invention seeks to provide a vaccine based on the currently circulating PCV2b subtype to achieve improved efficacy and protection.
Key aspects include the generation of a chimeric PCV1-2b virus, which is shown to be attenuated and non-pathogenic in susceptible pigs, yet elicits strong protective and cross-protective immunity against both PCV2a and PCV2b viral challenges. The chimeric virus may be administered in varied forms, including as a live attenuated, inactivated vaccine, or through delivery of corresponding nucleic acid constructs. The invention also details methods of vaccinating and protecting pigs from PCV2 infection and associated disease through administration of these compositions.
Claims Coverage
There are two independent inventive features in the patent claims, focused on methods of immunizing pigs against PCV2 infection and protecting them against porcine circovirus-associated disease using a defined chimeric PCV1-2b vaccine.
Method of immunizing a pig against PCV2 using a chimeric PCV1-2b vaccine
This inventive feature is a method that comprises administering to a pig an immunologically effective amount of a viral vaccine. The vaccine includes a physiologically acceptable carrier and an immunogenic amount of a chimeric PCV1-2b virus. Key characteristics include: - The chimeric PCV1-2b comprises a nucleic acid molecule encoding a nonpathogenic virus derived from the genomic sequence of PCV1. - The open reading frame 2 (ORF2) from a wild-type PCV2b strain (having the sequence SEQ ID NO: 2) replaces the ORF2 capsid gene in PCV1. - The method covers administration of either live attenuated or inactivated chimeric PCV1-2b virus.
Method of protecting a pig against porcine circovirus-associated disease (PCVAD) using a chimeric PCV1-2b vaccine
This inventive feature is a method of protecting a pig against PCVAD by administering an immunologically effective amount of a viral vaccine that includes a chimeric PCV1-2b. Main highlights involve: - The vaccine formulation comprises a physiologically acceptable carrier and an immunogenic amount of a chimeric PCV1-2b virus. - The chimeric virus contains a nucleic acid encoding the nonpathogenic PCV1-2b, wherein ORF2 from the wild-type PCV2b replaces the ORF2 capsid gene of PCV1. - Administration routes and forms (live attenuated or inactivated) are encompassed within the described methods.
In summary, the claims broadly cover immunization and disease protection methods for pigs utilizing a chimeric nonpathogenic PCV1-2b virus, specifically defined by the substitution of the PCV1 capsid gene with ORF2 from a wild-type PCV2b strain.
Stated Advantages
The chimeric PCV1-2b virus is attenuated and nonpathogenic in pigs, providing a safer alternative for vaccination compared to traditional live vaccines.
The invention induces both protective and cross-protective immunity against PCV2b and PCV2a subtypes, offering broad protection against prevalent disease strains.
The live virus vaccine is genetically stable, making it easier to manufacture, store, and deliver than other types of attenuated vaccines.
The vaccine can be administered in different forms, including live, inactivated, or as infectious DNA, providing flexible options for immunization.
The chimeric vaccine is effective at reducing or preventing viremia, lesions, and severity of PCVAD compared to unvaccinated controls.
Documented Applications
Immunizing pigs against PCV2 viral infection using a chimeric PCV1-2b vaccine.
Protecting pigs against porcine circovirus-associated disease (PCVAD) by administering a chimeric PCV1-2b vaccine.
Offering both live attenuated and inactivated vaccine forms for porcine circovirus immunization.
Providing cross-protection in pigs against both PCV2a and PCV2b subtypes.
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