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      The Haemophilus influenzae HtrA protein is a protective antigen.

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          Abstract

          The htrA gene from two strains of nontypeable Haemophilus influenzae has been cloned and sequenced, and the encoded approximately 46-kDa HtrA proteins were found to be highly conserved. H. influenzae HtrA has approximately 55% identity with the Escherichia coli and Salmonella typhimurium HtrA stress response proteins, and expression of the H. influenzae htrA gene was inducible by high temperature. Recombinant HtrA (rHtrA) was expressed from E. coli, and the purified protein was found to have serine protease activity. rHtrA was found to be very immunogenic and partially protective in both the passive infant rat model of bacteremia and the active chinchilla model of otitis media. Immunoblot analysis indicated that HtrA is antigenically conserved in encapsulated and nontypeable H. influenzae species. Site-directed mutagenesis was performed on the htrA gene to ablate the endogenous serine protease activity of wild-type HtrA, and it was found that eight of nine recombinant mutant proteins had no measurable residual proteolytic activity. Two mutant proteins were tested in the animal protection models, and one, H91A, was found to be partially protective in both models. H91A HtrA may be a good candidate antigen for a vaccine against invasive H. influenzae type b disease and otitis media and is currently in phase I clinical trials.

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          Author and article information

          Journal
          Infect Immun
          Infection and immunity
          American Society for Microbiology
          0019-9567
          0019-9567
          Mar 1998
          : 66
          : 3
          Affiliations
          [1 ] Pasteur Merieux Connaught Canada Research, North York, Ontario. sloosmore@ca.pmc-vacc.com
          Article
          10.1128/IAI.66.3.899-906.1998
          107993
          9488373
          55768be8-29b5-4b41-9da5-30bb0f366245
          History

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