Use of pertussis toxin encoded by ptx genes from Bordetella bronchiseptica to model the effects of antigenic drift of pertussis toxin on antibody neutralization.
Recently, concern has been voiced about the potential effect that antigenic divergence of circulating strains of Bordetella pertussis might have on the efficacy of pertussis vaccines. In order to model antigenic drift of pertussis toxin, a critical component of many pertussis vaccines, and to examine the effects of such drift on antibody neutralization, we engineered a strain of B. pertussis to produce a variant pertussis toxin molecule that contains many of the amino acid changes found in the toxin encoded by Bordetella bronchiseptica ptx genes. This altered form of the toxin, which is efficiently secreted by B. pertussis and which displays significant biological activity, was found to be neutralized by antibodies induced by vaccination as readily as toxin produced by wild-type B. pertussis. These findings suggest that significant amino acid changes in the pertussis toxin sequence can occur without drastically altering the ability of antibodies to recognize and neutralize the toxin molecule.
Hausman
S Z
SZ
Laboratory of Respiratory and Special Pathogens, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Burns
D L
DL
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001884:Bordetella / Q000235:genetics / Q000276:immunology*; D016950:Bordetella bronchiseptica / Q000235:genetics / Q000276:immunology; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology; D005798:Genes, Bacterial; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000276:immunology*; D014917:Whooping Cough / Q000517:prevention & control
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D010567:Pertussis Vaccine; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin