The molecular engineering of pertussis toxoid.
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.
Burnette
W N
WN
Amgen Inc., Thousand Oaks, CA 91320.
Mar
V L
VL
Bartley
T D
TD
Kaslow
H R
HR
Cieplak
W
W
Keith
J M
JM
Sato
H
H
Burns
D L
DL
Arciniega
J L
JL
Shahin
R D
RD
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
D010567:Pertussis Vaccine; D014121:Toxoids; D014614:Vaccines, Synthetic; C051093:pertussis toxoid