City of Hope

Other

John A Zaia

John J Rossi

Hema Pande

Arthur D Riggs

Edouard M Cantin

Ghislaine Hawkins

Brian R Clark

R Bruce Wallace

Pairoj Chang

George J Murakawa

Terrence D Giugni

Cecilia S&ouml;derberg

Erna Moller

A process for identifying a viral RNA nucleotide sequence present in a sample of peripheral blood cells which comprises amplifying such RNA simultaneously with at least one other RNA nucleotide sequence present in a virus infected cell in said sample, and thereafter separately and sequentially analyzing the amplification reaction products with probes homologous with authentic RNA and with such other RNA sequence to identify one or both of said RNA nucleotide sequences.

Method for amplification and detection of RNA sequences

This invention relates to mutated CMVpp65, a viral structural protein which activates cell mediated immunity in humans infected with CMV. The mutations remove undesirable protein kinase activity naturally present in the protein and make it suitable for the production of both DNA and protein vaccines. Therefore, the invention provides proteins and DNAS, as well as vaccines comprising the proteins and DNAs, including cellular vaccines and vectors. Other embodiments of the invention relate to methods of enhancing immune response and vaccinating against CMV, including gene therapy methods and vectors.

Protein kinase deficient, immunologically active CMVpp65 mutants

This invention relates to mutated CMVpp65, a viral structural protein which activates cell mediated immunity in humans infected with CMV. The mutations remove undesirable protein kinase activity naturally present in the protein and make it suitable for the production of both DNA and protein vaccines. Therefore, the invention provides proteins and DNAs, as well as vaccines comprising the proteins and DNAs, including cellular vaccines and vectors. Other embodiments of the invention relate to methods of enhancing immune response and vaccinating against CMV, including gene therapy methods and vectors.

A method for the prevention or treatment of human cytomegalovirus is described. Aminopeptidases, preferably in soluble form is administered exogenously to the patient. The invention involves the discovery that aminopeptidases are a CMV surface protein involved in post-binding events in the CMV infection process. The invention includes the discovery that AP, including specifically APN, on the surface of the virion and on the surface of the cell is involved in the CMV infection process.

Treatment of cytomegalovirus using aminopeptidase N

Disclosed are amino acid sequences of the late 64 kilodalton protein of human cytomegalovirus (HCMVgp64), useful in diagnosing and preventing HCMV infections.

Method for detection and prevention of human cytomegalovirus infection

Immunogens for use in human cytomegalovirus vaccines or skin tests which comprise human cytomegalovirus matrix proteins or fractions thereof are disclosed. It is also disclosed that such matrix proteins are target antigens for human cytomegalovirus specific cytotoxic T-lymphocytes.

Induction of cytolytic T-lymphocytes with cytomegalovirus polypeptides

A DNA probe has been isolated which is capable of hybridizing to an oligonucleotide sequence coding for a polypeptide from a major 64 Kilodalton protein of human cytomegalovirus (HCMVgp64). The probe has a sequence of at least seventeen (17) to as many as seven hundred twenty-one (721) nucleotides. The DNA fragments coding for the major late protein of human cytomegalovirus (HCMVgp64) may be hybridized to DNA fragments of HCMV DNA from an individual having human cytomegalovirus infection. The major late protein of human cytomegalovirus (HCMVgp64) also reacts with T-lymphocytes of an individual after natural infection of that individual with human cytomegalovirus. Thus, the HCMVgp64 protein may be used as a vaccine to prevent HCMV infection.

Ribozymes useful to cleave HIV-1 and other viral or endogenous cellular RNAs are disclosed. Also disclosed are transformed cells which express such ribozymes and human AIDS therapy involving the administration of such ribozymes.

Ribozyme cleavage of HIV RNA

Stable, catalytic efficient ribozymes useful, inter alia, to cleave HIV-I RNA or any other viral or endogenous cellular RNA, in vitro and in vivo, cells transformed with such ribozymes and the use of such ribozymes and cells for anti-AIDs therapy are disclosed.

Ribozyme cleavage of HIV-I RNA

A method of inhibiting human immunodeficiency virus (HIV) comprising administering a therapeutically effective amount of an antiviral agent to attack the first splice acceptor site of the tat III gene of HIV.

Oligonucleotide phosphonates and method of inhibiting a human

A DNA probe has been isolated which is capable of hybridizing to an oligonucleotide sequence coding for a polypeptide from a major 64 Kilodalton protein of human cytomegalovirus (HCMVgp64). The probe has a sequence of at least seventeen (17) to as many as seven hundred twenty-one 721) nucleotides. The probe may be labelled as by radioactivity. The probe has been used to screen DNA fragments constituting a subgenomic library of human cytomegalovirus DNA to obtain DNA fragments coding for the major late protein of human cytomegalovirus. The DNA fragments coding for the major late protein of human cytomegalovirus (HCMVgp64) may be hybridized to DNA fragments of HCMV DNA from an individual having human cytomegalovirus infection. The viral DNA can be used as whole HCMV DNA or as fragments formed by digesting the human cytomegalovirus DNA with a restriction endonuclease such as one of the restriction endonucleases EcoRI, BamHI, XbaI, HindIII and PrtI. During the screening of clinical specimens, the DNA fragment coding for HCMVgp64 of human cytomegalovirus hybridizes to whole HCMV DNA or to a particular one of the DNA fragments produced by digesting the human cytomegalovirus DNA with the restriction endonucleases. As a resuslt of such hybridization, the identity of human cytomegalovirus may be established. The particular DNA fragment may have a map location of approximately 0.50 to 0.51 units in the human cytomegalovirus (strain Towne) genome. It may have a sequence of about 721 nucleotides. The major late protein of human cytomegalovirus (HCMVgp64) also reacts with T-lymphocytes of an individual after natural infection of that individual with human cytomegalovirus. Thus, the HCMVgp64 protein may be used as a vaccine to prevent HCMV infection.

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Arcadia, CA, United States of America

John A Zaia