HYPEREXPRESSION SYSTEM FOR RECOMBINANT BCG VACCINES

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$50,000.00
Award Year:
1992
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Agency Tracking Number:
18947
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
Medimmune Inc
35 West Watkins Mill Road, Gaithersburg, MD, 20878
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Charles K Stover
(301) 417-0770
Business Contact:
() -
Research Institution:
n/a
Abstract
BCG, A LIVE ATTENUATED STRAIN OF MYCOBACTERIUM BOVIS, OFFERS A NUMBER A DISTINCT ADVANTAGES AS A LIVE RECOMBINANT VACCINE VEHICLE. THESE ADVANTAGES INCLUDE POTENT ADJUVANT ACTIVITY AND AHISTORY OF SAFE USE IN HUMANS AS A TUBERCULOSIS VACCINE. MAJOR GENETIC OBSTACLES IMPEDING THE DEVELOPMENT OF BCG AS A VACCINE VEHICLE HAVE NOW BEEN LARGELY OVERCOME WITH THE DEVELOPMENT OF ESCHERICHIA COLI/MYCOBACTERIAL SHUTTLE VECTORS. RECENT IMMUNOGENICITY STUDIES WITH SEVERAL RECOMBINANT BCG-BASED VACCINES ARE PROMISING AND SUGGEST THAT HIGH-LEVEL EXPRESSION OF TARGET ANTIGEN MAY CONTRIBUTE TO ITS ANTIGEN IMMUNODOMINANCE IN THE COMPLEX BACKGROUND OF MYCOBACTERIAL PROTEINS. SINCE IT HAS BEEN OBSERVED THAT CONSTITUTIVE HIGH-LEVEL EXPRESSION OF SOME FOREIGN ANTIGENS IN BCG IS DELETERIOUS TO THE BCG HOST STRAIN, WE WILL DEVELOP A BCG VECTOR/HOST SYSTEM INCORPORATING BCG STRESS PROMOTERS WITH TRANSCRIPTIONAL COMPONENTS FROM BACTERIOPHAGE T7 (T7 RNA POLYMERASE) AND THE E. COLI LACTOSE OPERON (LAC REPRESSOR AND OPERATOR TO REGULATE THE HIGH-LEVEL SYNTHESIS OF RECOMBINANT ANTIGENS IN BCG. IN ADDITION TO PROVIDINGAN INEXPENSIVE SOURCE OF ANTIGEN IN AN IMMUNOGENIC FORMAT WITHOUT ANTIGEN PURIFICATION, IT IS ALSO POSSIBLE THAT THE BCG/T7 SYSTEM COULD PROVIDE AN ALTERNATIVE TO LIVE RECOMBINANT BCG VACCINES WHICH MIGHT NOT BE SUITABLE IN IMMUNOCOMPROMISED INDIVIDUALS.

* information listed above is at the time of submission.

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