Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant virus encoding one or more heterologous proteins...
Patent
1994-03-28
1997-05-06
Mosher, Mary E.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant virus encoding one or more heterologous proteins...
4242051, 4242291, 424 9321, 4352351, A61K 39245, A61K 39295, C12N 700, C12N 510
Patent
active
056268505
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention is concerned with a live herpesvirus vaccine.
BACKGROUND OF THE INVENTION P Currently, several types of herpesvirus
vaccines are being applied, i.e. inactivated virus vaccines, subunit vaccines and modified live virus (MLV) vaccines.
Inactivated virus vaccines have the advantage that they do not comprise live infective viral material obviating the possibility of reversion of the viruses to a virulent state.
However, inactivated virus vaccines and subunit vaccines require the production of large quantities of the active vaccine component and are expensive to produce. Furthermore, these types of vaccines also require several inoculations with the vaccine in the presence of an adjuvant in order to provide immunity which is effective and long lasting.
MLV vaccines have important advantages in that they induce a rapid and long lasting immune response, both humoral and cellular, without the need of large quantities of the active component in the absence of adjuvants.
However, these vaccines still bear the risk of the vaccine virus being shed into the environment by the vaccinated animal, in particular when the live vaccine is administered via the natural route, e.g. intranasally.
Although MLV vaccines have been proven to be safe and efficacious there is a risk that the vaccine viruses revert to a more virulent state, or that the MLV spreads to other animals which are more susceptible for the MVL vaccine virus.
In particular, for the purpose of risk assessment by regulatory authorities with respect to vaccines based on genetically modified organisms, especially live organisms expressing foreign genes, the aspect of possible shedding of these organisms in the environment is very important.
Thus, it can be appreciated that herpesvirus vaccines which display the advantages of live virus inoculation but which are confined to the vaccinated animals are highly desirable.
The envelope glycoproteins of herpesviruses are major targets of the immune response to herpes vital infection. Furthermore, these glycoproteins are important for the interaction of the virus with its host cell.
The pseudorabies virus (PRV) is a herpesvirus that causes an economically significant disease in swine called Aujeszky's disease. It has been well documented that the glycoprotein D (gD) homolog of PRV (glycoprotein 50, gp50) is a major immunogen of PRV which is the most potent for the induction of protective immunity in an infected host animal (Eloit, M. et al., Archs. Virol. 99, 45-56, 1988; Marchioli, C. et al., Am. J. Vet.res. 49, 860-864, 1988; Ishii, H. et al., J. Gen. Virol. 69, 1411-1414, 1988; Marchioli, C. C. et al., J. Virol. 61, 3977-3982, 1987; Wathen, M. W. et al., J. Virol. 51, 57-62, 1984, Mettenleiter, T. C., Comp. Immun. Microbiol. Infect. Dis. 14, 151-163, 1991).
Furthermore, Rauh, I. and Mettenleiter, T. C. (J. Virol. 65, 5348-5356, 1991), and Peeters, B. et al., (J. Virol. 66, 894-905, 1992) constructed a gp50-negative (gp50-) PRV mutant which is phenotypically gp50-positive as result of their growth in a cell line expressing gp50. It was concluded therein that for the in vitro replication of the virus gp50 is essential for penetration into a cell and is not required for cell-cell spread of the virus.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a live herpesvirus vaccine which is both effective in that it induces a protective immune response and safe because of a reduced level of shedding live viruses in the environment, thereby combining the potency of a MLV vaccine and the safety of an inactivated vaccine.
The invention is characterized in that the live herpesvirus vaccine comprise live herpesviruses which are not able to produce a functional gD homolog said herpesviruses being complemented with the gD homolog.
With gD homolog herein is meant the glycoprotein of the specific herpesvirus which exhibits significant homology to the well characterized glycoprotein D of the herpes simplex virus (HSV). Several herpesvirus gD homologs and the ge
REFERENCES:
patent: 5240703 (1993-08-01), Cochran
Samulski, R.J. et al. 1989. Journal of Virology, vol. 63, pp. 3822-3828.
Morgenstern, J.P. et al. 1990. Nucleic Acids Research, vol. 18, pp. 3587-3596.
C. Marchioli et al., "Evaluation of pseudirabies virus glycoprotein gp50 as a vaccine for Aujesky's disease in mice and swine," J. Virol., vol. 61, No. 12, pp. 3977-3982, 1987.
D. Johnson et al., "Herpes Simplex viruses lacking glycoprotein D are unable inhibit virus penetration," J. Virol. vol. 62, No. 12, pp. 4605-4612, 1988.
B. Peeters et al., "Envelope glycoprotein gp50 of pseudorabies virus is essential for virus entry," J. Virol., vol. 67, No. 1, pp. 170-177, 1993.
I. Rauh et al., "Pseudorabies glcoproteins gII and gp50 are essential for virus penetration," J. Virol., vol. 65, No. 10, pp. 5348-5356, 1991.
B. Peeters et al., "Pseudorabies virus envelope glycoproteins are essential for virus penetration," J. Virol., vol. 66, No. 2, pp. 894-905, 1992.
N. De Wind et al., "Linker insertion mutagenesis of herpesvirus," J. Virol. vol. 64, No. 1o, pp. 4691-4696, 1990.
S. Heffner et al., "Glycoprotein gp50 negative pseudorabies virus," J. Virol., vol. 67, No. 3, pp. 1529-1537, 1993.
De, B.K. et al. 1988. Vaccine vol. 6 pp. 257-261.
Mettenleiter Thomas C.
van Woensel Petrus A. M.
Visser Nicolaas
Akzo Nobel N.V.
Gormley Mary E.
Mosher Mary E.
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