Patent ID: 6040427
Filing Date: 2000-03-21
Classification: A61K,C07K

Abstract:
An isolated DNA molecule comprising a recombinant coding sequence encoding a Bordetella pertussis holotoxin comprising a modified B-oligomer comprising either or both of a modified dimer D1or D2 wherein said modified dimer comprises an unmodified S4 subunit and either a modified S2 subunit or a modified S3 subunit and said modified B-oligomer optionally comprises an unmodified S5 subunit and further optionally comprises an unmodified S1 subunit, wherein said holotoxin comprising a modified B-oligomer is specifically reactive with antisera capable of recognizing a wild-type Bordetella pertussis holotoxin having no modified subunits;wherein said modified S2 subunit comprises one or more amino acid sequence modifications selected from the group consisting of a deletion of one or more of Tyr.sup.102, Tyr.sup.103 and Asn.sup.105, an amino acid substitution of either or both of Tyr.sup.102 and Tyr.sup.103 and a substitution of a negatively-charged amino acid for Asn.sup.105 ; andwherein said modified S3 subunit comprises one or more amino acid sequence modifications selected from the group consisting of a deletion of one or more of Tyr.sup.102, Tyr.sup.103 and Lyr.sup.105, an amino acid substitution of either or both of Tyr.sup.102 and Tyr.sup.103, and a substitution of a negatively-charged amino acid for Lys.sup.105.