title: The molecular engineering of pertussis toxoid.
abstract: The demand for a safer pertussis vaccine has led to the development of acellular vaccine products. We have sought to manufacture a component vaccine based upon the genetic inactivation of pertussis toxin derived by recombinant DNA technology and protein engineering. Rational site-directed mutagenesis of the S1 subunit of pertussis toxin has resulted in an enzymatically-deactivated polypeptide which retains its immunogenic potential. Mutagenic analysis of the other subunits of this toxin has permitted a delineation of the structural determinants involved in its recognition of cellular receptors. The in vitro assembly of holotoxin species possessing selectively engineered subunits may facilitate the production of a molecularly-defined genetic toxoid for pertussis prophylaxis.
authors.affiliation: Amgen Inc., Thousand Oaks, CA 91320.
authors.forename: W N
authors.initials: WN
authors.lastname: Burnette
authors.forename: V L
authors.initials: VL
authors.lastname: Mar
authors.forename: T D
authors.initials: TD
authors.lastname: Bartley
authors.forename: H R
authors.initials: HR
authors.lastname: Kaslow
authors.forename: W
authors.initials: W
authors.lastname: Cieplak
authors.forename: J M
authors.initials: JM
authors.lastname: Keith
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: D L
authors.initials: DL
authors.lastname: Burns
authors.forename: J L
authors.initials: JL
authors.lastname: Arciniega
authors.forename: R D
authors.initials: RD
authors.lastname: Shahin
mesh_terms: D005818:Genetic Engineering; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010567:Pertussis Vaccine / Q000302:isolation & purification; D014121:Toxoids / Q000235:genetics*; D014614:Vaccines, Synthetic / Q000302:isolation & purification; D014917:Whooping Cough / Q000517:prevention & control
chemical_list: D010567:Pertussis Vaccine; D014121:Toxoids; D014614:Vaccines, Synthetic; C051093:pertussis toxoid