Human cytomegalovirus DNA constructs and uses therefor

Details Human cytomegalovirus DNA constructs and uses therefor Human cytomegalovirus DNA constructs and uses therefor

1999-01-19

2002-09-10

Scheiner, Laurie (Department: 1648)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C435S069100, C435S320100, C424S230100

Reexamination Certificate

active

06448389

ABSTRACT:

FIELD OF THE INVENTION
This invention relates generally to compositions useful in preventing and treating human cytomegalovirus infection.
BACKGROUND OF THE INVENTION
Cytomegalovirus (CMV) is one of a group of highly host specific herpes viruses that produce unique large cells bearing intranuclear inclusions. The envelope of the human cytomegalovirus (HCMV) is characterized by a major glycoprotein complex termed gB or gCI, which was previously referred to as gA.
Infection with HCMV is common and usually asymptomatic. However, the incidence and spectrum of disease in newborns and immunocompromised hosts establishes this virus as an important human pathogen. HCMV has also been suggested to be an important co-factor in the development of atherosclerosis and restenosis after angioplastic surgery.
Several HCMV vaccines have been developed or are in the process of development. Vaccines based on live attenuated strains of HCMV have been described. [See, e.g., S. A. Plotkin et al,
Lancet,
1:528-30 (1984); S. A. Plotkin et al,
J. Infect. Dis.,
134:470-75 (1976); S. A. Plotkin et al, “Prevention of Cytomegalovirus Disease by Towne Strain Live Attenuated Vaccine”, in Birth Defects, Original Article Series, 20(1):271-287 (1984); J. P. Glazer et al,
Ann. Intern. Med.;
91:676-83 (1979); and U.S. Pat. No. 3,959,466.] A proposed HCMV vaccine using a recombinant vaccinia virus expressing HCMV glycoprotein B has also been described. [See, e.g., Cranage, M. P. et al,
EMBO J.,
5:3057-3063 (1986).] However, vaccinia vaccines are considered possible causes of encephalitis. Other recombinant HCMV vaccines have been described. See, e.g., G. S. Marshall et al,
J. Infect. Dis.,
162:1177-1181 (1990); K. Berencsi et al,
J. Gen. Virol.,
74:2507-2512 (1993), which describe adenovirus-HCMV recombinants.
There remains a need in the art for additional compositions useful in preventing CMV infection by enhancing immune responses to HCMV vaccines and generating neutralizing antibody and/or cellular responses to CMV in the human immune system.
SUMMARY OF THE INVENTION
The present invention provides a series of DNA molecules expressing human cytomegalovirus (HCMV) genome fragments, which are particularly useful in inducing HCMV-specific immune responses.
Thus, in one aspect, the invention provides a DNA molecule which is non-replicating in mammals and which comprises at least one human cytomegalovirus antigen which is operably linked to regulatory sequences which express the antigen in the mammal. Advantageously, the antigen elicits an immune response in said mammal. In one preferred embodiment, the DNA molecule is a plasmid.
In another aspect, the invention provides a plasmid, pTet-gB, containing the portion of the HCMV genome (UL55) encoding gB. This plasmid further contains a tetracycline regulatable HCMV-immediate early promoter, which is useful in controlling expression of gB. Another plasmid of the invention encoding the full-length gB subunit protein is a p&Dgr;RC-gB plasmid.
Yet another plasmid of the invention, p&Dgr;RC-gB
680
, contains the portion of the HCMV genome encoding the N-terminal 680 amino acids of the gB protein (gB
1-680
).
The p&Dgr;RC-pp65 plasmid of the invention contains the portion of the HCMV genome (UL83) encoding the HCMV pp65 tegument protein. The p&Dgr;RC-pp150 plasmid contains the portion of the HCMV genome (UL32) encoding the HCMV pp150 tegument protein.
The p&Dgr;RC-exon-4 contains the portion of the HCMV genome (truncated UL123) encoding HCMV immediate-early (IE) exon-4.
In yet another aspect, the present invention provides an immunogenic composition of the invention comprising at least one of the DNA molecules of the invention and a carrier.
In still another aspect, the present invention provides a method of inducing HCMV-specific immune responses in an animal by administering to the animal an effective amount of an immunogenic composition of the invention. Preferably, this composition contains p&Dgr;RC-gB
680
, pTet-gB and/or p&Dgr;RC-pp65.
In yet a further aspect, the present invention provides a method of priming immune responses to a selected human cytomegalovirus immunogenic composition by administering an immunogenic composition of the invention prior to administration of the second immunogenic or vaccine composition.
Other aspects and advantages of the present invention are described further in the following detailed description of the preferred embodiments thereof.


REFERENCES:
patent: 3959466 (1976-05-01), Plotkin
patent: 4689225 (1987-08-01), Pereira
patent: 4920209 (1990-04-01), Davis
patent: 5124440 (1992-06-01), Gehrz
patent: 5552143 (1996-09-01), Plotkin
patent: 5591439 (1997-01-01), Plotkin
patent: 180288 (1986-05-01), None
patent: 236145 (1987-09-01), None
patent: 252302 (1988-01-01), None
patent: 252531 (1988-01-01), None
patent: 268014 (1988-05-01), None
patent: 271201 (1988-06-01), None
patent: 277773 (1988-08-01), None
patent: 389286 (1990-09-01), None
patent: 609580 (1994-08-01), None
patent: WO89/07143 (1989-08-01), None
patent: WO90/00062 (1990-01-01), None
patent: WO90/01497 (1990-02-01), None
patent: WO90/06771 (1990-06-01), None
patent: WO90/11302 (1990-10-01), None
patent: WO91/02004 (1991-02-01), None
patent: WO91/18088 (1991-11-01), None
patent: WO92/00323 (1992-01-01), None
patent: WO92/02628 (1992-02-01), None
patent: WO93/19191 (1993-09-01), None
patent: WO94/17810 (1994-08-01), None
patent: WO94/23744 (1994-10-01), None
patent: WO96/01321 (1996-01-01), None
patent: WO97/40165 (1997-10-01), None
Plachter, B., et al., 1990, “Procaryotic expression of phosphorylated tegument protein pp65 of human cytomegalovirus and application of recombinant peptides for immunoblot analyses”, J. Clin. Microbiol. 28(6):1229-1235.*
Pande, H., et al., 1991, “Human cytomegalovirus strain Towne pp65 gene: nucleotide sequence and expression inEscherichia coli”, Virol. 182:220-228.*
Pande, H., et al., 1995, “Direct DNA immunization of mice with plasmid DNA encoding the tegument protein pp65 (ppUL83) of human cytomegalovirus induces high levels of circulating antibody to the encoded protein”, Scandanav. J. Infect. Dis. 99:117-20.*
Hayashi, I., et al., 1993, “A point mutation of alanine 163 to threonine is responsible for the defective secretion of high molecular weight kininogen by the liver or brown Norway Katholiek rats”, J. Biol. Chem. 268(23):17219-17224.*
Baier, G., et al., 1994, “An efficient expression, purification, and immunodetection system for recombinant gene products”, Bio Tech. 17(1):94, 96, 98, and 99.*
Ulmer, J. B., et al., 1994, “Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines”, Vaccine 12(16):1541-1544.*
Invitrogen catalog, 1994, p. 51.*
M. Cranage et al, “Identification of the Human Cytomegalovirus Glycoprotein B Gene and Induction of Neutralizing Antibodies via its Expression in Recombinant Vaccinia Virus”,EMBO J.,5(11):3057-3063 (Nov., 1986).
K. Berencsi et al, “Murine Cytotoxic T Cell Response Specific for Human Cytomegalovirus Glycoprotein B (gB) Induced by Adenovirus and Vaccinia Virus Recombinants Expressing gB”,J. Gen. Virol.,74(11):2507-2512 (Nov., 1993) [Berencsi I].
S. Plotkin et al, “Towne-Vaccine-Induced Prevention of Cytomegalovirus Disease After Renal Transplants”,Lancet,1:528-530 (Mar. 10, 1984) [Plotkin I].
S. Plotkin et al, “Prevention of Cytomegalovirus Disease by Towne Strain Live Attenuated Vaccine”,Birth Defects: Original Article Series,20(1):271-287 (1984) [Plotkin II].
S. Plotkin et al, “Clinical Trials of Immunization with the Towne 125 Strain of Human Cytomegalovirus”,J. Infect. Dis.,134(5):470-475 (Nov., 1976) [Plotkin III].
J. Glazer et al, “Live Cytomegalovirus Vaccination of Renal Transplant Candidates”,Annals of Internal Medicine,91:676-683 (Nov., 1979).
E. Gonczol et al, “Preclinical Evaluation of an ALVAC (canarypox)-Human Cytomegalovirus Glycoprotein B Vaccine Candidate”,Vaccine,13(12):1080-1085 (1995) [Gonczol I].
K. Berencsi et al, “The N-terminal 303 Amino Acids of the Human Cytomegalovirus

Affiliated with

Also associated with

Rating

Human cytomegalovirus DNA constructs and uses therefor does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Human cytomegalovirus DNA constructs and uses therefor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Human cytomegalovirus DNA constructs and uses therefor will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2837783