Antigenic heterogeneity of immunoglobulin A1 proteases from encapsulated and non-encapsulated Haemophilus influenzae

Abstract

Indirect evidence suggests that immunoglobulin A1 (IgA1) proteases may be factors in the pathogenesis of certain infectious diseases, including meningitis, gonorrhoea, and destructive periodontitis. Bacterial IgA1 proteases are therefore potential candidates as vaccines. In this study, IgA1 proteases from 166 clinical isolates and reference strains of Haemophilus influenzae and Haemophilus aegyptius were compared with regard to specific activity and pattern of enzyme inhibition by antisera raised against IgA1 protease from nine selected strains of H. influenzae. A total of 93% of H. influenzae strains and all H. aegyptius strains had detectable IgA1 protease activity. The majority of strains cleaved a prolyl-seryl or a prolyl-threonyl peptide bond in the alpha 1 hinge region, whereas occasional H. influenzae strains possessed two separate IgA1 proteases with these two specific activities. Of the 155 IgA1 protease-producing strains, all except 12 could be assigned to one of 14 IgA1 protease "inhibition types," each defined by a characteristic pattern of inhibition by the nine antisera. There was no correlation between IgA1 protease type and biotype of the strains. However, among 92 encapsulated H. influenzae strains, a close correlation between capsular serotype and IgA1 protease type was observed. With the exception of serotype f, strains of all capsular serotypes produced an exclusive antigenic type of IgA1 protease. All 38 strains of serotype b produced IgA1 protease of inhibition type 1, which was never demonstrated in non-encapsulated H. influenzae strains. These results facilitate the detection of an antibody response against specific IgA1 proteases and are of practical value for a possible future vaccine against H. influenzae serotype b infections.

Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence

“…Examination of IgAl proteases from a large number of isolates of the species listed in Fig. 1 by the use of neutralizing antisera raised in rabbits has disclosed a remarkable antigenic diversity, most notable among H. infrueniue and S. pneumoniue IgAl proteases (66,76,78,80). IgAl proteases of the two pathogenic Neisseriu species show less diversity detectable with neutralizing antisera and share the same protease "inhibition types" in agreement with their close genetic relationship (79,80).…”

Molecular determinants of the pathogenesis of disease due to non-typable Haemophilus influenzae

“…Examination of large numbers of typable and nontypable strains of H. in£uenzae has established that almost all strains express an IgA1 protease [50,58,64,70,71]. Initial experiments attempted to classify H. in£uenzae strains based on the type of IgA1 protease produced and identi¢ed four broad categories: production of a type 1 protease, production of a type 2 protease, production of both type 1 and type 2 proteases, or production of no protease (uncommon).…”

“…Initial experiments attempted to classify H. in£uenzae strains based on the type of IgA1 protease produced and identi¢ed four broad categories: production of a type 1 protease, production of a type 2 protease, production of both type 1 and type 2 proteases, or production of no protease (uncommon). Kilian et al further classi¢ed IgA1 protease-positive strains into categories based on the ability of the IgA1 protease from a particular strain to cleave IgA1 after incubation with inhibitory antiserum prepared against nine di¡erent IgA1 proteases [70]. These investigators found that the IgA1 proteases from type b strains were relatively conserved and grouped into only one of 15 inhibition types.…”

Molecular determinants of the pathogenesis of disease due to non-typableHaemophilus influenzae

“…Examination of large numbers of typable and non‐typable strains of H. influenzae has established that almost all strains express an IgA1 protease [50, 58, 64, 70, 71]. Initial experiments attempted to classify H. influenzae strains based on the type of IgA1 protease produced and identified four broad categories: production of a type 1 protease, production of a type 2 protease, production of both type 1 and type 2 proteases, or production of no protease (uncommon).…”

“…Initial experiments attempted to classify H. influenzae strains based on the type of IgA1 protease produced and identified four broad categories: production of a type 1 protease, production of a type 2 protease, production of both type 1 and type 2 proteases, or production of no protease (uncommon). Kilian et al further classified IgA1 protease‐positive strains into categories based on the ability of the IgA1 protease from a particular strain to cleave IgA1 after incubation with inhibitory antiserum prepared against nine different IgA1 proteases [70]. These investigators found that the IgA1 proteases from type b strains were relatively conserved and grouped into only one of 15 inhibition types.…”