title: A phase I clinical study of a live attenuated Bordetella pertussis vaccine--BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male volunteers.
abstract: BACKGROUND
  Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins.
  
  
  METHODS
  We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 10³, 10⁵ or 10⁷ colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination.
  
  
  RESULTS
  Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups.
  
  
  CONCLUSIONS
  BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01188512.
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Rigmor
authors.initials: R
authors.lastname: Thorstensson
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Birger
authors.initials: B
authors.lastname: Trollfors
authors.affiliation: Karolinska Trial Alliance, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Nabil
authors.initials: N
authors.lastname: Al-Tawil
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maja
authors.initials: M
authors.lastname: Jahnmatz
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Bergström
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Margaretha
authors.initials: M
authors.lastname: Ljungman
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Törner
authors.affiliation: Swedish Institute for Communicable Disease Control, Solna, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Wehlin
authors.affiliation: Q-Biologicals, BioIncubator, Zwijnaarde, Belgium.
authors.forename: Annie
authors.initials: A
authors.lastname: Van Broekhoven
authors.affiliation: Q-Biologicals, BioIncubator, Zwijnaarde, Belgium.
authors.forename: Fons
authors.initials: F
authors.lastname: Bosman
authors.affiliation: Inserm, Lille, France ; National Center for Scientific Research, Lille, France ; Université Lille-Nord de France, Lille, France ; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.affiliation: Inserm, Lille, France ; National Center for Scientific Research, Lille, France ; Université Lille-Nord de France, Lille, France ; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mielcarek
authors.affiliation: Inserm, Lille, France ; National Center for Scientific Research, Lille, France ; Université Lille-Nord de France, Lille, France ; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D001886:Bordetella pertussis / Q000276:immunology* / Q000302:isolation & purification; D015169:Colony Count, Microbial; D003710:Demography; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D007109:Immunity / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D009305:Nasopharynx / Q000382:microbiology / Q000473:pathology; D010567:Pertussis Vaccine / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D010919:Placebos; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D014917:Whooping Cough / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D010567:Pertussis Vaccine; D010919:Placebos; D014613:Vaccines, Attenuated