title: B-cell responses after intranasal vaccination with the novel attenuated Bordetella pertussis vaccine strain BPZE1 in a randomized phase I clinical trial.
abstract: Despite high vaccination coverage, pertussis is still a global concern in infant morbidity and mortality, and improved pertussis vaccines are needed. A live attenuated Bordetella pertussis strain, named BPZE1, was designed as an intranasal vaccine candidate and has recently been tested in man in a phase I clinical trial. Here, we report the evaluation of the B-cell responses after vaccination with BPZE1. Forty-eight healthy males with no previous pertussis-vaccination were randomized into one of three dose-escalating groups or into a placebo group. Plasma blast- and memory B-cell responses were evaluated by ELISpot against three different pertussis antigens: pertussis toxin, filamentous haemagglutinin and pertactin. Seven out of the 36 subjects who had received the vaccine were colonized by BPZE1, and significant increases in the memory B-cell response were detected against all three tested antigens in the culture-positive subjects between days 0 and 28 post-vaccination. The culture-positive subjects also mounted a significant increase in the filamentous haemagglutinin-specific plasma blast response between days 7 and 14 post-vaccination. No response could be detected in the culture-negatives or in the placebo group post-vaccination. These data show that BPZE1 is immunogenic in humans and is therefore a promising candidate for a novel pertussis vaccine. This trial is registered at ClinicalTrials.gov (NCT01188512).
authors.affiliation: Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: maja.jahnmatz@folkhalsomyndigheten.se.
authors.forename: Maja
authors.initials: M
authors.lastname: Jahnmatz
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Amu
authors.affiliation: Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Margaretha
authors.initials: M
authors.lastname: Ljungman
authors.affiliation: Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Wehlin
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
authors.affiliation: Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; University Lille Nord de France, Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mielcarek
authors.affiliation: Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; University Lille Nord de France, Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.affiliation: Public Health Agency of Sweden, Solna, Sweden.
authors.forename: Rigmor
authors.initials: R
authors.lastname: Thorstensson
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001886:Bordetella pertussis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D008297:Male; D010567:Pertussis Vaccine / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D010567:Pertussis Vaccine; D014613:Vaccines, Attenuated
keywords: B cells; BPZE1; Live attenuated nasal vaccine; Novel human vaccine; Pertussis; Phase I clinical trial