ATTENUATION OF THE NYCBH VACCINE STRAIN OF VACCINIA SIMULATION MODELING OF THE IMMUNE SYSTEM

IN ORDER TO CREATE A VACCINE STRAIN ATTENUATED FOR VIRULENCE, THREE STRAINS OF VACCINIA VIRUS, THE NEW YORK CITY BOARD OF HEALTH VACCINE STRAIN AND TWO MORE VIRULENT DERIVATIVES, THE WESTERN RESERVE AND THE INTERNATIONAL HEALTH DEPARTMENT J STRAINS, WILL BE USED TO PREPARE RECOMBINANT VIRUSES DELETED FOR SPECIFIC FUNCTIONS. THE GENES SELECTED FOR DELETION ENCODE FUNCTIONS WHICH: 1) ARE RESPONSIBLE FOR THE ABILITY OF THE VIRUS TO REPLICATE IN NON-DIVIDING CELLS; 2) CONTRIBUTE TO THE MECHANISM OF VIRUS RELEASE FROM INFECTED CELLS; OR 3) ARE DEFINED BY A NATURALLY OCCURRING DELETION. THE PURIFIED RECOMBINANTS WILL BE ANALYZED FOR GROWTH IN TISSUE CULTURE AS EFFICIENT PARTICLE PRODUCTION WILL BE REQUIRED FOR SUBSEQUENT ANIMAL STUDIES AND COMMERCIALIZATION. CONCURRENTLY, THE THREE PARENTAL STRAINS WHICH DIFFER IN THEIR VIRULENCE WILL BE UTILIZED TO INVESTIGATE THE ROLE OF DIFFERENT ROUTES OF INOCULATION IN INBRED STRAINS OF MICE AS THEY RELATE TO VIRAL SPREAD AND LETHALITY. THE PURPOSE IS TO DEVELOP A PERTINENT AND EFFICIENT ANIMAL MODEL SYSTEM IN ORDER TO ASSESS THE EFFECTS OF SPECIFIC GENOMIC ALTERATIONS ON THE VIRULENCE OF VACCINIA VIRUS. THE ULTIMATE GOAL OF THESE STUDIES IS TO PREPARE A SERIES OF STABLE ATTENUATED STRAINS FOR HUMAN VACCINE TRIALS. NO UNIVERSALLY ACCEPTED MODEL OF THE IMMUNE SYSTEM EXISTS, THEREFORE NO SUBSTANTIAL MODEL OF THE DISEASED STATES OF MANEXISTS EITHER. MAN'S DISEASES--CANCER, AUTO IMMUNITY (ARTHRITIS), SEVERE ALLERGIES AND RECENTLY AIDS, ALL INVOLVE THE IMMUNE SYSTEM AND WOULD BENEFIT FROM HAVING A DEFINED MODEL OF THE DISEASED STATE. TRANSPLANTATION OF CELLS AND TISSUES AND IMMUNOSUPPRESSIVE DRUG THERAPY BOTH WOULD GAIN A GIANT STEP FORWARD IF A SIMULATION MODEL OF THE IMMUNE SYSTEM WERE AVAILABLE. THIS APPLICATION WILL TEST THE FEASIBILITY OF BUILDING SUCH A MODEL, EXPLORING AVAILABLE SYSTEMS AND METHODS FOR EFFECTIVELY BUILDING AN IMMUNE SYSTEM SIMULATION MODEL. OUR GOAL IS TO BUILD A PROTOTYPE OF THE MODEL USING A SEGMENT OF THE IMMUNE SYSTEM AND IN THE LONG TERM INTEGRATING THE ENTIRE IMMUNE SYSTEM. WE WILL USE OBJECT-ORIENTED ARTIFICIAL INTELLIGENCE METHODS,INTEGRATED WITH ICON GRAPHIC INTERFACES AND RULE-BASED TECHNIQUES.