title: Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes.
abstract: Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVs(BpPagL)) are good vaccine candidates to protect against pertussis. In this work the OMVs(BpPagL) formulated with diphtheria and tetanus toxoids (Tdap(OMVsBpPagL)) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims BALB/c mice were immunized with Tdap(OMVsBpPagL) and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of Tdap(OMVsBpPagL) were performed. With the normalized doses of both vaccines we observed that Tdap(OMVsBpPagL) protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the Tdap(OMVsBpPagL) protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results Tdap(OMVsBpPagL) induced Th1 and Th2 immune response. In contrast, commercial Tdap induced Th2 but weak Th1 responses. All results presented here showed that Tdap(OMVsBpPagL) is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: María Emilia
authors.initials: ME
authors.lastname: Gaillard
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bottero
authors.affiliation: Laboratorio de Investigaciones del Sistema Inmune (LISIN), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calles 47 y 115, 1900, La Plata, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: Errea
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ormazábal
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Zurita
authors.affiliation: Laboratorio de Investigaciones del Sistema Inmune (LISIN), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calles 47 y 115, 1900, La Plata, Argentina.
authors.forename: Griselda
authors.initials: G
authors.lastname: Moreno
authors.affiliation: Laboratorio de Investigaciones del Sistema Inmune (LISIN), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calles 47 y 115, 1900, La Plata, Argentina.
authors.forename: Martin
authors.initials: M
authors.lastname: Rumbo
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: Celina
authors.initials: C
authors.lastname: Castuma
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: Erika
authors.initials: E
authors.lastname: Bartel
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina.
authors.forename: Dario
authors.initials: D
authors.lastname: Flores
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Laboratory for Infectious Diseases and Screening (LIS) Centre for Infectious Disease Control, Bilthoven, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Laboratory for Infectious Diseases and Screening (LIS) Centre for Infectious Disease Control, Bilthoven, The Netherlands.
authors.forename: Arno
authors.initials: A
authors.lastname: van der Ark
authors.affiliation: Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata. Calles 50 y 115, 1900, La Plata, Argentina. Electronic address: hozbor.daniela@gmail.com.
authors.forename: Daniela
authors.initials: D
authors.lastname: F Hozbor
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001886:Bordetella pertussis / Q000145:classification* / Q000235:genetics; D056738:Cross Protection; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000276:immunology*; D005260:Female; D005838:Genotype; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D022282:Vaccines, Acellular / Q000276:immunology; D014917:Whooping Cough / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D011994:Recombinant Proteins; D022282:Vaccines, Acellular; D037342:Pertussis Toxin
keywords: Acellular vaccines; Bordetella pertussis; OMVs; Whooping cough