IMMUNOGLOBULIN A1 PROTEASES (IGA1 PROTEASES), METHOD OF GENE-TECHNOLOGICALLY PRODUCING THIS TYPE OF ENZYME AND VACCINES CONTAINING THE ENZYMES AND FRAGMENTS THEREOF FOR IMMUNIZING AGAINST BACTERIAL MENINGITIS AND OTHER DISEASES CAUSED BY IGA1 PROTEASE-PRODUCING BACTERIA

摘要

Secretion of IgA1 proteases is a characteristic of Haemophilus influenzae and several other bacterial pathogens causing infectious diseases, including meningitis. Indirect evidence suggests that the proteases are important virulence factors. The iga gene encoding IgA1 protease, especially that from H. influenzae serotype b, has been cloned into Escherichia coli in which the recombinant iga gene was expressed and the resulting protease secreted. Sequencing a part of a 7.5 kb DNA fragment containing the iga gene revealed a large open reading frame (ORF) with a strongly biased codon usage and having the potential of encoding a protein of 1541 amino acids and a molecular mass of 169 kd. Putative promoter and terminator elements flanking the ORF have been identified. Comparing the deduced amino acid sequence of the produced H. influenzae IgA1 protease with that of a similar protease from Neisseria gonorrhoeae reveals several domains with a high degree of homology. Analogous to mechanisms known from the N. gonorrhoeae IgA protease secretion, there is proposed a scheme of post-translational modifications of the H. influenzae IgA1 protease precursor leading to a secreted protease with a molecular mass of 108 kd which is close to the Mr 100 kd estimated for the mature IgA1 protease.