title: Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough.
abstract: Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth.
authors.affiliation: 1INSERM U629, Lille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mielcarek
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.forename: Dominique
authors.initials: D
authors.lastname: Raze
authors.forename: Julie
authors.initials: J
authors.lastname: Bertout
authors.forename: Carine
authors.initials: C
authors.lastname: Rouanet
authors.forename: Amena Ben
authors.initials: AB
authors.lastname: Younes
authors.forename: Colette
authors.initials: C
authors.lastname: Creusy
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Engle
authors.forename: William E
authors.initials: WE
authors.lastname: Goldman
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
mesh_terms: D000281:Administration, Intranasal; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D001886:Bordetella pertussis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007114:Immunization / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D012137:Respiratory System / Q000382:microbiology / Q000473:pathology; D022282:Vaccines, Acellular / Q000008:administration & dosage / Q000627:therapeutic use; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000627:therapeutic use; D014917:Whooping Cough / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D022282:Vaccines, Acellular; D014613:Vaccines, Attenuated