| Autor: |
Loosmore, Sheena M., Yang, Yan-ping, Oomen, Ray, Shortreed, Jean M., Coleman, Debbie C., Klein, Michel H. |
| Zdroj: |
Infection and Immunity; March 1998, Vol. 66 Issue: 3 p899-906, 8p |
| Abstrakt: |
ABSTRACTThe htrAgene from two strains of nontypeableHaemophilus influenzaehas been cloned and sequenced, and the encoded approximately 46-kDa HtrA proteins were found to be highly conserved. H. influenzaeHtrA has approximately 55% identity with the Escherichia coliand Salmonella typhimuriumHtrA stress response proteins, and expression of theH. influenzae htrAgene 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. influenzaespecies. Site-directed mutagenesis was performed on the htrAgene 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. influenzaetype b disease and otitis media and is currently in phase I clinical trials. |
| Databáze: |
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