Chemistry: molecular biology and microbiology – Vector – per se
Reexamination Certificate
2001-03-27
2004-09-07
Park, Hankyel T. (Department: 1648)
Chemistry: molecular biology and microbiology
Vector, per se
C435S069100, C435S069200, C424S093200
Reexamination Certificate
active
06787351
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to replication deficient adenovirus vectors comprising an optimized human immunodeficiency virus (HIV) gag gene under the control of a strong promoter, which are suitable for vaccines against HIV.
BACKGROUND OF THE INVENTION
Human Immunodeficiency Virus-1 (HIV-1) is the etiological agent of acquired human immune deficiency syndrome (AIDS) and related disorders.
Vaccination is an effective form of disease prevention and has proven successful against several types of viral infection. However, determining ways to present HIV-1 antigens to the human immune system in order to evoke protective humoral and cellular immunity is a difficult task. In AIDS patients, free virus is present in low levels only. Transmission of HIV-1 is enhanced by cell-to-cell interaction via fusion and syncytia formation. Hence, antibodies generated against free virus or viral subunits are generally ineffective in eliminating virus-infected cells.
European Patent Applications 0 638 316 (Published Feb. 15, 1995) and 0 586 076 (Published Mar. 9, 1994), (both assigned to American Home Products Corporation) describe replicating adenovirus vectors carrying an HIV gene, including env or gag. Various treatment regimens were used with chimpanzees and dogs, some of which included booster adenovirus or protein plus alum treatments.
Infection with HIV-1 is almost always fatal, and at present there are no cures for HIV-1 infection. Effective vaccines for prevention of HIV-1 infection are not yet available. Because of the danger of reversion or infection, live attenuated virus probably cannot be used as a vaccine, and. subunit vaccine approaches have not been successful at preventing HIV infection. Treatments for HIV-1 infection, while prolonging the lives of some infected persons, have serious side effects. There is thus a great need for effective treatments and vaccines to combat this lethal infection.
SUMMARY OF THE INVENTION
This invention relates to a vaccine composition comprising a replication-defective adenoviral vector comprising at least one gene encoding an HIV gag protein, wherein the gene comprises codons optimized for expression in a human, and the gene is operably linked to a heterologous promoter.
Another aspect of this invention relates to an adenoviral vaccine vector comprising: a replication defective adenoviral genome, wherein the adenoviral genome does not have a functional E1 gene, and the adenoviral genome further comprises a gene expression cassette comprising:
i) a nucleic acid encoding a HIV gag protein, wherein the nucleic acid is codon optimized for expression in a human host;
ii) a heterologous promoter is operatively linked to the nucleic acid encoding the gag protein; and
iii) a transcription terminator.
In preferred embodiments, the E1 gene has been deleted from the adenoviral vector, and the HIV expression cassette has replaced the deleted E1 gene. In other preferred embodiments, the replication defective adenovirus genome does not have a functional E3 gene, and preferably the E3 gene has been deleted.
This invention also relates to a shuttle plasmid vector comprising: an adenoviral portion and a plasmid portion, wherein said adenovirus portion comprises: a) a replication defective adenovirus genome which does not have a functional E1 gene; and b) a gene expression cassette comprising: a nucleic acid encoding an HIV gag protein, wherein the nucleic acid is codon optimized for expression in a human host; a heterologous promoter operably linked to the nucleic acid encoding the gag protein; and a transcription terminator.
Other aspects of this invention include a host cell comprising the adenoviral vaccine vectors and/or the shuttle plasmid vectors, methods of producing the vectors comprising introducing the adenoviral vaccine vector into a host cell which expresses adenoviral E1 protein, and harvesting the resultant adenoviral vaccine vectors.
Another aspect of this invention is a method of generating a cellular immune response against an HIV protein in an individual comprising administering to the individual an adenovirus vaccine vector comprising:
a) a replication defective adenoviral vector, wherein the adenoviral vector does not have a functional E1 gene, and b) a gene expression cassette comprising: i) a nucleic acid encoding, an HIV gag protein, wherein the nucleic acid is codon optimized for expression in a human host; ii) a heterologous promoter operatively linked to the nucleic acid encoding the gag protein; and iii) a transcription terminator.
In some embodiments of this invention, the individual is given more than one administration of adenovirus vaccine vector, and it may be given in a regiment accompanied by the administration of a plasmid vaccine. The plasmid vaccine comprises a plasmid encoding a codon-optimized gag protein, a heterologous promoter operably linked to the gag protein nucleic acids, and a transcription terminator. There may be a predetermined minimum amount of time separating the, administrations. The individual can be given a first dose of plasmid vaccine, and then a second dose of plasmid vaccine. Alternatively, the individual may be given a first dose of adenovirus vaccine vector, and then a second dose of adenoviral vaccine vector. In other embodiments, the plasmid vaccine is administered first, followed after a time by administration of the adenovirus vector vaccine. Conversely, the adenovirus vaccine vector may be administered first, followed by administration of plasmid vaccine after a time. In these embodiments, an individual may be given multiple doses of the same adenovirus serotype in either viral vector or plasmid form, or the virus may be of differing serotypes.
REFERENCES:
patent: 5643579 (1997-07-01), Hung et al.
patent: 5672508 (1997-09-01), Gyuris et al.
patent: 5716613 (1998-02-01), Guber et al.
patent: 5859193 (1999-01-01), Devare et al.
patent: 6019978 (2000-02-01), Ertl et al.
patent: 6033908 (2000-03-01), Bout et al.
patent: 6287571 (2001-09-01), Ertl et al.
patent: 0 586 076 (1993-07-01), None
patent: 0 638 316 (1994-07-01), None
patent: 0 707 071 (1995-08-01), None
patent: WO96/21015 (1996-07-01), None
patent: WO96/39178 (1996-12-01), None
patent: WO97/00326 (1997-01-01), None
patent: WO97/31115 (1997-08-01), None
patent: WO97/39771 (1997-10-01), None
patent: WO97/48370 (1997-12-01), None
patent: WO98/34640 (1998-08-01), None
patent: WO98/56919 (1998-12-01), None
patent: WO01/21201 (2000-09-01), None
patent: WO01/02067 (2001-01-01), None
patent: WO01/43693 (2001-06-01), None
patent: WO01/45748 (2001-06-01), None
Chroboczek, J. et al. “The Sequence of the Genome of Adenovirus Type 5 and Its Comparison with the Genome of Adenovirus Type 2”, 1992, Virology, vol. 186, pp. 280-285.
Hitt, M. et al. “Human Adenovirus Vectors for Gene Transfer into Mammalian Cells”, 1997, Advances in Pharmacology, vol. 40, pp. 137-206.
Graham, F. et al. “Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5”, 1977, J. Gen. Virol., vol. 36, pp. 59-74.
Myers, G. et al. “Human Retroviruses and AIDS 1995 : A compilation and Analysis of Nucleic Acid and Amino Acid Sequences”, 1995, Part II, A3-A19.
Chapman, B. et al. “Effect of intron A from human cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells”, 1991, Nucleic Acids Resarch, vol. 19, pp. 3979-3986.
Montgomery, D. et al. “Heterologous and Homologous Protection Against Influenza A by DNA Vaccination: Optimization of DNA Vectors”, 1993, DNA and Cell Biology, vol. 12, pp. 777-783.
Grable, M. et al. “Adenovirus Type 5 Packaging Domain Is Composed of a Repeated Element That is Functionally Redundant”, Journal of Virology, 1990, vol. 64, pp. 2047-2056.
Grable, M. et al. “cis and trans Requirements for the Selective Packaging of Adenovirus Type 5 DNA”, Journal of Virology, 1992, vol. 66, pp. 723-731.
Wang, Y. et al. “The Use of an E1-Deleted, Replication-Defective Adenovirus Recombinant Expressing the Rabies Virus Glycoprotein for Early Vaccination of Mice against Rabies Virus”, Journal of Virology, 199
Bett Andrew J.
Casimiro Danilo R.
Caulfield Michael J.
Chastain Michael A.
Chen Ling
Cocuzzo Anna L.
Merck & Co. , Inc.
Park Hankyel T.
Tribble Jack L.
LandOfFree
Adenovirus carrying gag gene HIV vaccine does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Adenovirus carrying gag gene HIV vaccine, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Adenovirus carrying gag gene HIV vaccine will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3204452