Virginia Tech Intellectual Properties, Inc.

Iowa State University Research Foundation, Inc.

Other

Wyeth Holdings Corporation

Solvay Animal Health, Inc.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Wyeth

Xiang-Jin Meng

Patrick G Halbur

Prem S Paul

Martijn Fenaux

Melissa A Lum

Yaowei Huang

Igor Morozov

Gholamreza Haqshenas

Fang-Fang Huang

Nathan M Beach

Young S Lyoo

Sheela Ramamoorthy

Robert H Purcell

Suzanne U Emerson

Yanyan Ni

Nathan Beach

Patrick Halbur

The present invention relates to infectious DNA clones, infectious chimeric DNA clones of porcine circovirus (PCV), vaccines and means of protecting pigs against viral infection or postweaning multisystemic wasting syndrome (PMWS) caused by PCV2. The new chimeric infectious DNA clone and its derived, avirulent chimeric virus are constructed from the nonpathogenic PCV1 in which the immunogenic ORF gene of the pathogenic PCV2 replaces a gene of the nonpathogenic PCV1, preferably in the same position. The chimeric virus advantageously retains the nonpathogenic phenotype of PCV1 but elicits specific immune responses against the pathogenic PCV2. The invention further embraces the immunogenic polypeptide expression products. In addition, the invention encompasses two mutations in the PCV2 immunogenic capsid gene and protein, and the introduction of the ORF2 mutations in the chimeric clones.

Chimeric infectious DNA clones, chimeric porcine circoviruses and uses thereof

The present invention also provides infectious DNA clones, biologically functional plasmid or viral vector containing the infectious nucleic acid genome molecule of Torque teno sus virus (TTsuV). The present invention also provides methods for diagnosing TTsuV infection via immunological methods, e.g., enzyme-linked immunoabsorbent assay (ELISA) and Western blot using PTTV specific antigens for detecting serum PTTV specific antibodies which indicate infections TTsuV1, TTsuV2, and individual TTsuV1 genotypes.

Infectious genomic DNA clone and serological profile of torque teno sus virus 1 and 2

The present invention provides four purified preparation containing a polynucleic acid molecule encoding porcine Torque teno virus (PTTV) genotypes or subtypes PTTV1a-VA, PTTV1b-VA, PTTV2b-VA, and PTTV2c-VA. The present invention also provides infectious DNA clones, biologically functional plasmid or viral vector containing the infectious nucleic acid genome molecule of the same. The present invention further provides live, attenuated, vector-expressed and purified recombinant capsid subunit or killed viral vaccines for protection against PTTV infection. The present invention additionally provides subunit vaccines comprising PTTV specific gene products, especially ORF1 capsid gene product for protection against PTTV infection. Further, the present invention provides methods for diagnosing PTTV infection via polymerase chain reaction (PCR) using specific primer for PTTV1, PTTV2, and individual PTTV1 genotypes. Finally, the present invention provides methods for diagnosing PTTV infection via immunological methods, e.g., enzyme-linked immunoabsorbent assay (ELISA) and Western blot using PTTV specific antigens for detecting serum PTTV specific antibodies.

Porcine torque teno virus vaccines and diagnosis

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).

Live attenuated chimeric porcine circovirus vaccine

The present invention provides a novel chimeric porcine circovirus infectious DNA clone and live attenuated chimeric virus with the PCV2, preferably of subtype PCV2, capsid gene integrated into a non-pathogenic PCV1 virus genome. In a particular embodiment, the PCV2 capids gene is of subtype PCV2, the predominant subtype circulating in pigs worldwide. The attenuated chimeric virus, designated PCV1-2, effectively protects pigs from PCV2challenges, and can be used as a live vaccine, as well as an inactivated (killed) vaccine, that provides protection and cross protection against PCV2and PCV2subtypes infection. The live attenuated vaccine of the present invention is also effective protecting pigs from porcine circovirus-associated disease (PCVAD).

Infectious genomic DNA clone and serological profile of Torque teno sus virus 1 and 2

The present invention provides a novel infectious cDNA clone of porcine reproductive and respiratory syndrome virus (PRRSV), particularly for PRRSV strain VR2385; an improved DNA-launched reverse genetics system for PRRSV; infectious chimeric PRRSV viruses generated through DNA shuffling; modified live-attenuated virus vaccines (MLV) using DNA shuffled chimeric viruses; chimeric viral proteins produced through shuffled chimeric viruses; PRRSV antigens and subunit vaccines based on shuffled chimeric viral proteins; and method of producing broadly protective PRRSV vaccines using DNA shuffling techniques.

Modified live-attenuated vaccines (MLV) created by DNA shuffling against porcine reproductive and respiratory syndrome virus (PRRSV)

The present invention relates to the cloning, identification and characterization of the unique and entire genomic sequences encoding new porcine DC-SIGN and LSECtin proteins, including the novel nucleotide sequences of the full-length cDNA and genes of both pDC-SIGN gene and pLSECtin. Also provided are the nucleic acid molecules encoding newly discovered porcine ICAM-3 isoforms from porcine monocyte-derived dendritic cells and the use thereof. Specifically, the invention is drawn to an isolated nucleic acid molecule comprising a nucleotide sequence encoding one or more of porcine DC-SIGN, porcine ICAM-3, porcine LSECtin, a complement of the nucleotide sequence or a functional, defined portion of the nucleotide sequence or a protein fusion product linked to a protein that may be of porcine or human origin. Methods for isolating and cloning the new porcine genes and for using the new nucleotide sequences in improved methods for propagating viruses, particularly enveloped viruses, are additionally described herein. The invention further includes new transfected cells or cell lines that can stably express the porcine proteins, new antibodies and the like.

Porcine DC-SIGN, ICAM-3 and LSECtin and uses thereof

The present invention relates to a novel isolated avian hepatitis E virus having a nucleotide sequence set forth in SEQ ID NO:1 or its complementary strand. The invention further concerns immunogenic compositions comprising this new virus or recombinant products such as the nucleic acid and vaccines that protect an avian or mammalian species from viral infection or hepatitis-splenomegaly syndrome caused by the hepatitis E virus. Also included in the scope of the invention is a method for propagating, inactivating or attenuating a hepatitis E virus comprising inoculating an embryonated chicken egg with a live, pathogenic hepatitis E virus and recovering the virus or serially passing the pathogenic virus through additional embryonated chicken eggs until the virus is rendered inactivated or attenuated. Further, this invention concerns diagnostic reagents for detecting an avian hepatitis E viral infection or diagnosing hepatitis-splenomegaly syndrome in an avian or mammalian species comprising an antibody raised or produced against the immunogenic compositions and antigens such as ORF2 proteins expressed in a baculovirus vector,, etc. The invention additionally encompasses methods for detecting avian HEV nucleic acid sequences using nucleic acid hybridization probes or oligonucleotide primers for polymerase chain reaction (PCR).

Avian hepatitis E virus, vaccines and methods of protecting against avian hepatitis-splenomegaly syndrome and mammalian hepatitis E

Growing community of inventors

Blacksburg, VA, United States of America

Xiang-Jin Meng