AN HAEMOPHILUS OMP AS A VACCINE CANDIDATE

VACCINATION IS THE MOST COST-EFFECTIVE MEANS OF PREVENTING HAEMOPHILUS INFLUENZAE TYPE B (HIB) DISEASE. NEWLY DEVELOPED HIB POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES BEING TESTED ARE EFFECTIVE IN CHILDREN 2 MONTHS AND OLDER. HOWEVER, SOME INFANTS MAY NOT BE ABLE TO RESPOND TO POLYSACCHARIDE ANTIGENS. A 15,000 DALTON PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN (PAL), IDENTIFIED AS A POTENTIAL VACCINE CANDIDATE, HAS BEEN FOUND IN ALL HIB ISOLATES TESTED. IN ADDITION, IT IS ANTIGENICALLY CONSERVEDAMONG HIB STRAINS. THE 15K PAL CONSTITUTES 1.5 PERCENT OF THE TOTAL OMPS, MAKING IT DIFFICULT AND EXPENSIVE TO PURIFY COMMERCIALLY. THESE STUDIES WILL FACILITATE PRODUCTION OF LARGE AMOUNTS OF THE PROTEIN FOR USE AS A VACCINE. THIS WOULD BE THE FIRST USE OF A PROTEIN VACCINE AGAINST HIB DISEASE. THESE STUDIES WILL USE RECOMBINANT PLASMIDS THAT ENCODE THE PUTATIVE 15K-PAL GENE IN ESCHERICHIA COLI TO OVEREXPRESS THE GENE PRODUCT, UNDER THE CONTROL OF A REGULATABLE PROMOTER. IMMUNOGENICITY OF THE CLONED PROTEIN WILL BE EXAMINED USING BOTH BACTERICIDAL ASSAYS AND ANIMAL PROTECTION STUDIES. PHASE II STUDIES WILL DEVELOP PROCEDURES AMENABLE TO LARGE-SCALE PURIFICATION OF THE CLONED PROTEIN AND ADDITIONAL IMMUNOGENICITY TESTING.