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

PLoS One. 2014 Jan 8;9(1):e83449. doi: 10.1371/journal.pone.0083449. eCollection 2014.

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.

Trial registration: ClinicalTrials.gov NCT01188512.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adult
  • Bordetella pertussis / immunology*
  • Bordetella pertussis / isolation & purification
  • Colony Count, Microbial
  • Demography
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Healthy Volunteers*
  • Humans
  • Immunity / immunology
  • Immunoglobulin G / blood
  • Male
  • Nasopharynx / microbiology
  • Nasopharynx / pathology
  • Pertussis Vaccine / adverse effects
  • Pertussis Vaccine / immunology
  • Pertussis Vaccine / therapeutic use*
  • Placebos
  • Vaccination
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Vaccines, Attenuated / therapeutic use*
  • Whooping Cough / blood
  • Whooping Cough / immunology*
  • Whooping Cough / microbiology
  • Whooping Cough / prevention & control*
  • Young Adult

Substances

  • Immunoglobulin G
  • Pertussis Vaccine
  • Placebos
  • Vaccines, Attenuated

Associated data

  • ClinicalTrials.gov/NCT01188512

Grant support

This work was supported by the European Commission Framework Program 7 (Child-Innovac project, grant agreement number 201502). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.