Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1998-11-20
2001-07-10
Wortman, Donna C. (Department: 1648)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C424S204100, C424S218100
Reexamination Certificate
active
06258788
ABSTRACT:
Tick-borne encephalitis (TBE) occurs over a wide area of Europe and the former Soviet Union. TBE is most frequently caused by infection with the flaviviruses Central European encephalitis (CEE) virus, or Russian spring summer encephalitis (RSSE) virus. These viruses are antigenically and genetically closely related to one another and often are considered to be subtypes of the same virus. However, two different tick vectors transmit RSSE and CEE viruses (
Ixodes persulcatus
and
Ixodes ricinus,
respectively) and RSSE virus generally causes a more severe disease than does CEE virus (reviewed in Monath, T. P. and F. X. Heinz, 1996, In B. N. Fields et al. (eds.)
Fields Virology,
Third Edition, Lippincott-Raven Publishers: Philadelphia, p. 961).
In parts of Europe, TBE cases have notably declined since the introduction in 1976 of a formalin-inactivated, chick embryo-derived vaccine. The vaccine is based on an Austrian strain of CEE virus, and elicited protective immunity in mice to the homologous CEE virus (strain Hypr) and to four strains of RSSE virus (Holzmann, H. et al., 1992,
Vaccine,
10, 345). Despite the success of this vaccine, it suffers the disadvantages commonly associated with inactivated virus vaccines such as the requirement for large-scale production and purification of a highly infectious human pathogen, the risk of incomplete inactivation of the virus, and the need to deliver the vaccine with adjuvant in a three-shot series (Kunz, C. F. et al., 1980,
J. Med. Virol.
6, 103). Also, this vaccine is not licensed for use in U.S. military personnel nor in U.S. travelers to TBE-endemic regions.
For these reasons, there is a need for an improved TBE vaccine.
SUMMARY OF THE INVENTION
The present invention satisfies the need discussed above. In this report, we describe two plasmid-based TBE candidate vaccines, which express the premembrane (prM) and envelope (E) genes of RSSE or CEE viruses under control of a cytomegalovirus early promoter. We chose the prM and E genes for expression because of earlier reports with other flaviviruses which indicated that coexpressed prM and E form subviral particles that are able to elicit neutralizing and protective immune responses in animals (Konishi, E. and P. W. Mason, 1993,
J. Virol.
67: 1672; Konishi, E. et al., 1992,
Virology
190:454; Pincus, S. et al., 1992,
Virology
187: 290). Coexpression of prM and E of CEE virus also produces subviral particles, and although these particles were not tested for immunogenicity, they were found to retain biological properties of complete virus such as membrane fusion and hemagglutination (Schalich, J. et al., 1996,
J. Virol.
70:4549).
To deliver our DNA vaccines, we chose to use the PowderJect-XR™ gene gun device described in WO 95/19799, Jul. 17, 1995. This instrument, which delivers DNA-coated gold beads directly into epidermal cells by high-velocity particle bombardment, was shown to more efficiently induce both humoral and cell-mediated immune responses, with smaller quantities of DNA, than inoculation of the same DNAs by other parenteral routes (Eisenbraun, M. et al., 1993,
DNA Cell. Biol.
12: 791; Fynan, E. F. et al., 1993,
Proc. Natl. Acad. Sci. U.S.A.
90: 11478; Haynes, J. R. et al., 1994,
AIDS Res. Hum. Retroviruses
10: Suppl. 2:S43; Pertmer, T. M. et al., 1995,
Vaccine
13: 1427). Epidermal inoculation of the DNA candidate vaccines also offers the advantages of gene expression in an immunologically active tissue that is generally exfoliated within 15 to 30 days, and which is an important natural focus of viral replication after tick-bite (Bos, J. D., 1997,
Clin. Exp. Immunol.
107 Suppl. 1:3; Labuda, M. et al., 1996,
Virology
219:357; Rambukkana, A. et al., 1995,
Lab. Invest.
73:521; Stingl, G., 1993,
Recent Results Cancer Res.
128:45). In this application we describe the elicitation of cross-protective immunity to RSSE and CEE viruses by DNA vaccines.
Therefore, the present invention relates to a method for eliciting in an individual an immune response against an alphavirus which causes tick-borne encephalitis comprising delivering to the individual a DNA vaccine comprising a vector including a viral antigen such that when the antigen is introduced into a cell from the individual, the DNA is expressed, the viral antigen is produced in the cell and an immune response against the antigen is mounted.
In one aspect of the invention, the DNA vaccine is delivered by coating a small carrier particle with the DNA vaccine and delivering the DNA-coated particle into an animal's epidermal tissue via particle bombardment. This method may be adapted for delivery to either epidermal or mucosal tissue, or delivery into peripheral blood cells, and thus may be used to induce humoral, cell-mediated, and secretory immune reponses in the vaccinated individual.
The DNA vaccine according to the present invention is inherently safe, is not painful to administer, and should not result in adverse side effects to the vaccinated individual. In addition, the invention does not require growth or use of tick-borne flavivirus, which may be spread by aerosol transmission and are typically fatal.
REFERENCES:
patent: 5204253 (1993-04-01), Sanford
patent: 5506125 (1996-04-01), McCabe
patent: 0691404 (1995-07-01), None
patent: 9519799 (1995-07-01), None
Colombage, G. et al. (1998) DNA-based and alphavirus-vectored immunisation with PrM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus. Virology 250, 151-163.
Schmaljohn, C. et al. (1997) Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge. J. Virol. 71, 9563-9568.
Konishi, E. et al. (1992) Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal infection. Virology 188, 714-720.
Pletnev, A. G. et al. (1986) Tick-borne encephalitis virus genome: The nucleotide sequence coding for virion structural proteins. FEBS 200, 317-321.
Wallner, G. et al. (1996) Characterization and complete genome sequences of high- and low-virulence variants of tick-borne encephalitis virus. J. Gen. Virol. 77, 1035-1042.
Schmaljohn et al., Evaluation of Tick-Borne Encephalitis DNA Vaccine in Monkeys. Virology 263:166-174, 1999.
Aberle et al., A DNA Immunization Model Study with Constructs Expressing the Tick-Borne Encephalitis Virus Envelope Protein E in Different Physical Forms. J. Immunol. 163(12):6756-6761, 1999.
Kozak, Marilyn; “The Scanning Model for Translation: An Update”, The J. of Cell Biology, vol. 108, Feb. 1989, pp. 229-241.
Heinz, “Characterization of Tick-Borne Encephalitus Virus and Immunogenicity of its Surface Components in Mice”, Acta Virol., 21:308-316 (1977).
Hambleton, et al., “Pathogenesis and Immune Response of Vaccinated and Unvaccinated Rhesus Monkeys to Tick-BOrne Encephalitis Virus”, Infection and Immunity, Jun. 1983, pp 995-1003.
Iacono-Connors, et al., “Characterization of Langat virus antigenic determinants defined by monoclonal antibodies to E, NS1 and preM and identification of a protective, non-neutralizing preM-specific monoclonal antibody”, Virus Research, 43 (1996), pp. 125-136.
Holzmann, et al., “A Single Amino Acid Substitution in Envelope Protein E of Tick-Borne Encephalitis Virus Leads to Attenuation i n the Mouse Model”, J. Virology, Oct. 1990, pp. 5156-5159.
Schalich, et al., “Recombinant Subviral Particles from Tick-Borne Encephalitis Virus are Fusogenic and Provide a Model System for Studying Flavivirus Envelope Glycoprotein Functions”, J. Virology, Jul. 1996, pp. 4549-4557.
Konishi, et al., “A Highly Attenuated Host Range-RestrictedVaccinia Virus Strain, NYVAC, Encoding the prM, E, and NS1 Genes of Japanese Encephalitis Virus Prevents JEV Viremia in Swine”, VIrology, 190, (1992) pp. 454-458.
Konishi and Mason, “Proper Muturation of the Japanese Encephalitis Virus Envelope Glycoprotein Requires Cosynthesis with the Premembrane Protein”, J. Virology,
Arwine Elizabeth
Harris Charles H.
The United States of America as represented by the Secretary of
Wortman Donna C.
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