Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Reexamination Certificate
1998-09-18
2001-10-23
Scheiner, Laurie (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
C435S320100
Reexamination Certificate
active
06306401
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to virology and disease control. Specifically, the present invention relates to mutated arthropod vectored viruses and their uses as vaccines.
2. Description of the Related Art
Arthropod vectored viruses (Arboviruses) are viral agents which are transmitted in nature by blood sucking insects. Many of these viruses have membrane bilayers with associated integral membrane proteins which make up the protective envelope of the virus particle (Togaviruses) (Schlesinger, S. and M. J. Schlesinger, 1990).
Collectively, the arthropod vectored viruses are second only to malaria as a source of insect-transmitted disease and death in man and animals throughout the world (Berge A. O. 1975). Among these viral agents are Eastern, Western, and Venezuelan Equine Encephalitis Viruses, Dengue Fever, Japanese Encephalititis, San Angelo Fever, and Yellow Fever. Further, diseases caused by these agents are in resurgence in North America (NIAID
Report of the Task Force on Microbiology and Infectious Diseases
1992, NIH Publication No. 92-3320) as a result of the introduction of the mosquito vector
Aedes albopictus
(Sprenger, and Wuithiranyagool 1985).
By their very nature, Arboviruses must be able to replicate in the tissues of both the invertebrate insect and the mammalian host (Brown, D. T., and L. Condreay, 1986, Bowers et al. 1995). Differences in the genetic and biochemical environment of these two host cell systems provide a basis for the production of viruses which can replicate in one host but not the other (Host Range Mutants).
Currently, Dengue Fever and Eastern Equine Encephalitis and other insect bourne viruses are in resurgence in the United States. The U.S. Army and other government agencies have been trying to make vaccines against these viruses since the 1960s with little success. Thus, the prior art is deficient in a vaccine against most arthropod vectored viruses and other membrane-coated viruses. The present invention fulfills this long-standing need and desire in the art.
SUMMARY OF THE INVENTION
One object of the present invention is to provide a genetically-engineered, membrane-enveloped virus, wherein the virus codes for a transmembrane protein which has a deletion of one or more amino acids such that the transmembrane protein is able to span the viral membrane when the engineered virus replicates in insect cells, but is unable to span the viral membrane when the virus replicates in mammalian cells. One embodiment of this object of the invention provides an Arthropod vectoral virus as the genetically-engineered, membrane-enveloped virus. Further, in preferred embodiments, the Arthropod vectoral virus may be selected from the group of Togaviruses, Flaviviruses and Bunya viruses and all other enveloped viruses which can replicate naturally in both mammalian and insect cells, as well as enveloped viruses which can be made to replicate in mammalian and insect cells by genetic engineering of either the virus or the cell.
In another embodiment of the present invention, there is provided a method of producing a viral vaccine from a genetically-engineered, membrane-bound virus for vaccination of mammals, comprising the steps of: engineering an amino acid deletion in a viral transmembrane protein to produce an engineered virus, wherein the transmembrane protein is able to span the membrane envelope when the engineered virus replicates in insect cells, but is unable to span the membrane envelope when the virus replicates in mammalian cells, and wherein the virus remains capable of replicating in insect cells; introducing the mutated virus into insect cells; and allowing the mutated virus to replicate in the insect cells to produce a viral vaccine.
In yet another embodiment of the present invention, there is provided a method for vaccination of an individual comprising the steps of: introducing the viral vaccine of the present invention into mammalian cells resulting in the non-productive infection of cells and tissues for immune surveillance.
Finally, the present invention also has the objective of providing a method of producing a viral vaccine from a genetically-engineered, membrane-bound virus to diseases spread by a wild mosquito population to mammals, comprising the steps of: engineering an amino acid deletion in a viral transmembrane protein to produce an engineered virus, wherein the transmembrane protein is able to span the membrane envelope when the engineered virus replicates in mosquito cells, but is unable to span the membrane envelope when the virus replicates in mammalian cells, and wherein the virus remains capable of replicating in wild mosquito cells; introducing the mutated virus into the wild mosquito population; and allowing the mutated virus to replicate in cells of the wild mosquito population to produce a population of mosquitos which harbor the vaccine strain of the virus and exclude the wild type (pathogenic) virus such that the mosquito bite delivers the vaccine to a mammal bitten.
Other and further aspects, features, and advantages of the present invention will be apparent from the following description of one of the presently preferred embodiments of the invention. These embodiments are given for the purpose of disclosure.
Brown Dennis T.
Hernandez Racquel
Parkin Jeffrey S.
Scheiner Laurie
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