title: Assessment of safety and efficacy against Bordetella pertussis of a new tetanus-reduced dose diphtheria-acellular pertussis vaccine in a murine model.
abstract: Tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model.
  
  
  
  Four-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice.
  
  
  
  Anti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P = 0.87 and P = 0.37, respectively). All leukocyte counts in the new vaccine group were within a mean ± 3 standard deviations range.
  
  
  
  A murine model involving a single dose primary DTaP vaccination followed by a single dose Tdap booster vaccination can be used for non-clinical studies of Tdap vaccines. The new Tdap vaccine manufactured in Korea exhibited comparable immunogenicity, protection efficacy, and safety with a commercially available Tdap vaccine.
authors.affiliation: Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kwon
authors.affiliation: Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Seung Beom
authors.initials: SB
authors.lastname: Han
authors.affiliation: The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Kyu Ri
authors.initials: KR
authors.lastname: Kang
authors.affiliation: The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Huh
authors.affiliation: Research Center, Green Cross Corporation, Yongin, Republic of Korea.
authors.forename: Gi Sub
authors.initials: GS
authors.lastname: Choi
authors.affiliation: Research Center, Green Cross Corporation, Yongin, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Ahn
authors.affiliation: Department of Pediatrics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. kjhan@catholic.ac.kr.|The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. kjhan@catholic.ac.kr.
authors.forename: Jin Han
authors.initials: JH
authors.lastname: Kang
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006388:Hemagglutinins; D006801:Humans; D007117:Immunization, Secondary; D000071497:Immunogenicity, Vaccine; D051379:Mice; D008810:Mice, Inbred C57BL; D037342:Pertussis Toxin; D056910:Republic of Korea; D010566:Virulence Factors, Bordetella / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D006388:Hemagglutinins; D010566:Virulence Factors, Bordetella; C048844:anti-IgG; C068929:pertactin; D037342:Pertussis Toxin
keywords: Diphtheria-tetanus-acellular pertussis vaccine; Efficacy; Immunogenicity; Mice; Safety