title: Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide.
abstract: A toxoid vaccine, composed of purified pertussis toxin inactivated with H2O2 (NICHD-Ptxd), was developed on the basis of evidence that serum neutralizing antibodies (antitoxin) would confer immunity to pertussis. In vivo and in vitro assays of NICHD-Ptxd showed only trace or nondetectable levels of pyrogenic, adenosine diphosphate-ribosyltransferase, binding and pharmacologic activities. Nevertheless, about 40% of the antigenicity of pertussis toxin was retained. Adult volunteers were injected, two times 6 weeks apart, with either 10 (n = 21), 50 (n = 25), or 75 (n = 30) micrograms/dose of one lot, Ptx-06, adsorbed onto AI(OH)3. Neither fever nor changes in the levels of leukocytes, lymphocytes, fasting blood glucose, or insulin were observed in the volunteers. The optimal immunizing dose, 50 micrograms, induced levels of antitoxin (geometric mean (GM) 302 U) comparable to those found in eight adults convalescent from pertussis (GM 269 U) and greater than those found in 18-month-old children after their fourth dose of diphtheria and tetanus toxoids and pertussis vaccine (GM 20.0 U, p less than 0.001). These data indicate that NICHD-Ptxd is safe and immunogenic in adults, and they justify its evaluation in infants and children.
authors.affiliation: Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: R D
authors.initials: RD
authors.lastname: Sekura
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Roberson
authors.forename: B
authors.initials: B
authors.lastname: Acton
authors.forename: B
authors.initials: B
authors.lastname: Trollfors
authors.forename: N
authors.initials: N
authors.lastname: Tolson
authors.forename: J
authors.initials: J
authors.lastname: Shiloach
authors.forename: D
authors.initials: D
authors.lastname: Bryla
authors.forename: J
authors.initials: J
authors.lastname: Muir-Nash
authors.forename: D
authors.initials: D
authors.lastname: Koeller
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D004168:Diphtheria Toxoid / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D037342:Pertussis Toxin; D010567:Pertussis Vaccine / Q000276:immunology / Q000494:pharmacology*; D013745:Tetanus Toxoid / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D004338:Drug Combinations; D010567:Pertussis Vaccine; D013745:Tetanus Toxoid; D010566:Virulence Factors, Bordetella; D006861:Hydrogen Peroxide; D037342:Pertussis Toxin