title: The diphtheria and pertussis components of diphtheria-tetanus toxoids-pertussis vaccine should be genetically inactivated mutant toxins.
abstract: Replacement of cellular with acellular pertussis (aP) vaccines has considerably reduced the systemic reactions observed with diphtheria-tetanus toxoids-pertussis vaccine but has not eliminated the extensive swelling (sometimes involving an entire limb) observed after the fifth injection of diphtheria-tetanus toxoids-aP (DTaP) vaccine. This local reaction, which is likely an Arthus hypersensitivity reaction caused by high levels of antibodies reacting with DTaP vaccine, could discourage its use in adults, who serve as the major reservoir of pertussis for infants. That a critical level of antibodies to pertussis toxin is both essential and sufficient to prevent infection with Bordetella pertussis is derived from data from animal and clinical studies, including data showing the similarities between the immunity induced by diphtheria and pertussis toxoids. The genetically inactivated diphtheria and pertussis mutant toxins are more immunogenic and, therefore, induce comparable levels of antitoxin at lower protein levels than do the formalin-treated native toxins. Replacement of the diphtheria and aP components with these improved antigens will reduce the amount of protein in DTaP vaccine and, most likely, the incidence and severity of local reactions in teenagers and adults.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. robbinsjo@mail.nih.gov
authors.forename: John B
authors.initials: JB
authors.lastname: Robbins
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
authors.forename: Birger
authors.initials: B
authors.lastname: Trollfors
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sato
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Keith
mesh_terms: D000328:Adult; D001183:Arthus Reaction / Q000209:etiology; D002648:Child; D002986:Clinical Trials as Topic; D004165:Diphtheria / Q000517:prevention & control; D004167:Diphtheria Toxin / Q000235:genetics* / Q000276:immunology; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007223:Infant; D009154:Mutation; D037342:Pertussis Toxin / Q000235:genetics* / Q000276:immunology; D013742:Tetanus / Q000517:prevention & control; D014611:Vaccination; D014917:Whooping Cough / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D004167:Diphtheria Toxin; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D037342:Pertussis Toxin