Over-expressing homologous antigen vaccine and a method of makin

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...

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4241841, 4242341, 4242481, 4242611, 4242001, 435 691, 435 693, 4351723, 4353201, 435243, 4352523, A61K 3902

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06149920&

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BRIEF SUMMARY
The invention pertains to an over-expressing homologous antigen vaccine, a method of producing the same, and a method of using the vaccine for prophylaxis or treatment of a vertebrate suffering from or at risk from a pathogen. The vaccine is derived from an attenuated or avirulent version of the pathogen, and over-expresses one or more genes from the pathogen, thereby providing immunity greater than that induced by a vaccine of the same pathogen without over-expression of a gene.


BACKGROUND OF THE INVENTION

Vaccines are used to protect against diseases, which are caused by pathogens. These pathogens are microbial organisms, such as bacteria and viruses, which affect animals, including humans. Vaccines are primarily derived from a pathogen by producing and administering either: a) an attenuated or avirulent version of the pathogen; b) the killed pathogen; c) extracted protective antigens or antigen mixes of the pathogen (homologous antigens); or d) a micro-organism expressing one or more protective antigens encoded by cloned genes originating in a microbial pathogen different from the vaccine strain (heterologous antigens).
Vaccines for both bacteria and viruses are engineered from microorganisms expressing one or more protective antigens, as described by K. Jones and M. Sheppard in Designer Vaccines, CRC Press (1997). Vaccines are intended to produce an immune response in the recipient consisting of at least one of an antibody mediated or T cell mediated immune response, thereby preventing future infection by a pathogen, or fighting a current pathogenic infection. In particular, vaccines against facultative intracellular pathogens, those growing inside the cells of the infected host, need to induce a strong and appropriate cell mediated immune response. In contrast, vaccines against obligate extracellular pathogens need to induce an appropriate antibody mediated immune response. Often, regardless of the pathogen, an appropriate combined antibody and cellular mediated immune response leads to sufficient protection or relief from infection. In order to achieve this protection or relief from infection, vaccines may express one or more homologous antigens, heterologous antigens, or a combination of both.
Vaccines may be administered to vertebrates both to prevent and treat infection by pathogens. Thus, vaccines are frequently administered to prevent the spread of a disease caused by a pathogen. In particular, herd animals, such as cows, goats, sheep and swine, are often vaccinated to prevent the spread of a disease among members of the herd. Further, because certain diseases may travel between vertebrates, including travel between various animals and between animals and humans, vaccines are used to prevent the spread of disease between various species, usually by administration to the infected animal and other uninfected animals in the immediate vicinity. However, other animals in the area which are less likely to contract the disease may also be vaccinated as a prophylactic measure. For example, an infected cow and its as yet uninfected herd may be vaccinated to treat a disease and prevent its further spread. As a prophylactic measure, other animals which are likely to contract the disease from the infected cow, such as neighboring cows, sheep or humans, may be vaccinated as well.
It has been found that vaccines derived from an attenuated or avirulent version of a pathogen are highly effective in preventing or fighting disease caused by that pathogen. In particular, it is known that such attenuated or avirulent pathogens can be modified to express heterologous antigens (antigens which are derived from a pathogen of a different species). In order to express heterologous antigens in a desired attenuated or avirulent pathogen, a gene encoding an antigen capable of providing protection against the pathogen is identified from the deoxyribonucleic acid of a heterologous species. The desired gene is isolated and then inserted into a plasmid capable of replication and expression in the attenuated or avirulent path

REFERENCES:
patent: 4888170 (1989-12-01), Curtiss, III
patent: 5468485 (1995-11-01), Curtiss, III
Ramesh Vamulpalli "Overexpression of Protective Antigen as a Novel Approach to Enhance Vaccine Efficacy of Brucella abortus Strain RB51" Infection and Immunity, vol. 68, No. 6, Jun. 2000, pp. 3286-3289.
Ramesh Vamulpalli "Brucella abortus Strain RB51 as a Vector for Heterologous Protein Expression and Induction of Specific Th1 Type Immune Responses" Infection and Immunity, vol. 68, No. 6, Jun. 2000, pp. 3290-3286.
Norman F. Cheville et al., "Effects Of Age At Vaccination On Efficacy Of Brucella abortus Strain RB51 To Protect Cattle Against Brucellosis,", Am. J. Vet. Res., vol. 587, No. 8, pp. 1153-1156, Aug. 1996.
Mark G. Stevens et al., "Lymphocyte Proliferation in Response to Brucella abortus RB51 and 2308 Proteins in RB51-Vaccinated or 2308-Infected Cattle," Infection and Immunity, vol. 64, No. 3, pp. 1007-1010, Mar. 1996.
P.H. Elzer et al., Antibody-mediated protection against Brucella abortus in BALB/c mice at successive periods after infection: variation between virulent strain 2308 and attenuated vaccine strain 19, Immunology, vol. 82, pp. 651-658, 1994.
Mark G. Stevens et al., "Role Of Immune Responses To A GroEL Heat Shock Protein In Preventing Brucellosis In Mice Vaccinated With Brucella Abortus Strain RB51," Comp. Immun. Microbiol. Infect. Dis. vol. 20, No. 2, pp. 147-153, Feb. 1997.
Boschiroli, M.L. et al., Protection Against Infection in Mice Vaccinated with a Brucella Abortus Mutant, Infection and Immunity, vol. 65, No. 2, pp. 798-800, Feb. 1997.

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