Pertussis toxin S1 mutant with reduced enzyme activity and a conserved protective epitope.
Pertussis toxin (PTX) is a major virulence factor in whooping cough and can elicit protective antibodies. Amino acid residues 8 to 15 of PTX subunit S1 are important for the adenosine diphosphate-ribosyltransferase activity associated with the pathobiological effects of PTX. Furthermore, this region contains at least a portion of an epitope that elicits both toxin-neutralizing and protective antibody responses in mice. The gene encoding the S1 subunit was subjected to site-specific mutagenesis in this critical region. A mutant containing a single amino acid substitution (Arg9----Lys) had reduced enzymatic activity (approximately 0.02% of control) while retaining the protective epitope. This analog S1 molecule may provide the basis for a genetically detoxified PTX with potential for use as a component of an acellular vaccine against whooping cough.
Burnette
W N
WN
Amgen, Thousand Oaks, CA 91320.
Cieplak
W
W
Mar
V L
VL
Kaljot
K T
KT
Sato
H
H
Keith
J M
JM
D001483:Base Sequence; D001886:Bordetella pertussis / Q000201:enzymology / Q000235:genetics; D003062:Codon; D000939:Epitopes / Q000235:genetics; D005796:Genes; D005798:Genes, Bacterial; D009154:Mutation; D009244:NAD+ Nucleosidase / Q000235:genetics / Q000378:metabolism; D009876:Operon; D037342:Pertussis Toxin; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D003062:Codon; D000939:Epitopes; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D011065:Poly(ADP-ribose) Polymerases; D037342:Pertussis Toxin; D009244:NAD+ Nucleosidase