The Phase I studies established the feasibility of using molecular approaches to derive from the NYCBH vaccine strain, stable attenuated mutants of unaltered immune efficacy. In this Phase II proposal selected mutants generated in the virulent NYCBH-IH isolate will be studied to determine their virulence parameters and immune protective capacity. An exhaustive study of virulence parameters in normal and immunocompromised mice will include, intracranial and intranasal LD50s, growth and dissemination from the site of inoculation, and the extent of pock formation on scarified skin. The immune protective capacity of mutants will be assessed by their ability to confer protection against a foreign pathogen by the expression of a single neutralizing antigen. The studies described above were performed for experimental convenience in a high virulence laboratory isolate of NYCBH. This information will be used to create specific mutations in a low virulence plaque purified isolate form the Wyeth vaccine seed stock (NYCBH-W) produced for the NIH under good manufacturing practice. The NYCBH-W mutants will be assessed for virulence parameters, and ability to confer protection against a foreign pathogen by the expression of a single neutralizing antigen. This data will be used to design first generation vaccine candidate(s) containing single mutations. Subsequently, combinations of mutations will be used to conform second generation vaccine candidate(s).

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI026028-03
Application #
3506036
Study Section
Special Emphasis Panel (SSS (B))
Project Start
1988-04-01
Project End
1991-12-04
Budget Start
1991-08-01
Budget End
1991-12-04
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Omnigene Diagnostics, Inc.
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02142