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SphB1 export system for antigen presentation to the respiratory tract by a live pertussis vaccine.

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Title: SphB1 export system for antigen presentation to the respiratory tract by a live pertussis vaccine.
Authors: Santiesteban-Lores LE; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France., Raze D; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France., Dubois V; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France.; Present Address: Glaxo SmithKline, 86, Rue de L'Institut, B-1330, Rixensart, Belgium., Tardy M; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France., Debrie AS; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France., Goldstein P; ILiAD Biotechnologies, Weston, FL, USA., Coutte L; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France. loic.coutte@inserm.fr., Locht C; University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL - Centre for Infection and Immunity of Lille, 1, Rue du Prof, F-59019, Calmette, Lille, France.
Source: Applied microbiology and biotechnology [Appl Microbiol Biotechnol] 2026 May 29; Vol. 110 (1). Date of Electronic Publication: 2026 May 29.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Springer International Country of Publication: Germany NLM ID: 8406612 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-0614 (Electronic) Linking ISSN: 01757598 NLM ISO Abbreviation: Appl Microbiol Biotechnol Subsets: MEDLINE
Imprint Name(s): Original Publication: Berlin ; New York : Springer International, c1984-
MeSH Terms: Pertussis Vaccine*/immunology , Pertussis Vaccine*/genetics , Pertussis Vaccine*/administration & dosage , Respiratory System*/immunology , Antigen Presentation*, Vaccines, Attenuated/immunology ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/administration & dosage ; Bordetella pertussis/immunology ; Bordetella pertussis/genetics ; Coronavirus Nucleocapsid Proteins/immunology ; Coronavirus Nucleocapsid Proteins/genetics ; Whooping Cough/prevention & control ; Whooping Cough/immunology ; CD8-Positive T-Lymphocytes/immunology ; Virulence Factors, Bordetella/genetics ; Immunoglobulin G/blood ; Animals ; Mice ; Female ; Mice, Inbred BALB C ; Protein Subunit Vaccines ; Administration, Intranasal ; Immunity, Mucosal ; Bacterial Outer Membrane Proteins
Abstract: BPZE1 is a live attenuated vaccine currently in advanced clinical development for nasal immunization against pertussis. The ability of this vaccine to induce mucosal and systemic, humoral and cellular immunity make it an attractive mucosal delivery system for heterologous antigens to induce immunity especially in the respiratory tract. Here, we have developed a heterologous antigen expression system based on the pertactin-deficient BPZE1 derivative IB-V002 by using the SphB1 secretion system to present the SARS-CoV-2 nucleocapsid protein (N) as a model antigen to the respiratory mucosa. SphB1 is an autotransporter comprising a subtilisin-like passenger domain and a C-terminal ß-barrel domain. The passenger domain was replaced by the SARS-CoV-2 N protein. The recombinant gene was inserted into the urease locus of IB-V002 and placed under the control of the pertactin promoter and signal peptide. Immunoblot analyses indicated that the chimeric protein was produced and secreted by the recombinant strain named BT-V101. Mice intranasally immunized with BT-V101 induced N-specific IgG in serum and IFN-γ production by spleen cells. Importantly, a local N-specific CD8+ T cell response was observed in nose-associated lymphoid tissues by MHC class I tetramer staining. Additionally, immunization with BT-V101 efficiently primed mice to recombinant purified N protein given as a boost either intranasally or subcutaneously. These results demonstrate the suitability of the B. pertussis SphB1 secretion machinery to secret heterologous antigens for the development of a mucosal immunization vaccine platform with the induction of specific humoral and cellular, local, and systemic immune responses. KEY POINTS: • The SphB1 export system was used to secrete heterologous antigens by B. pertussis. • Recombinant B. pertussis induced systemic and local immunity to foreign antigens. • Recombinant B. pertussis efficiently primed immune responses to foreign antigens.
(© 2026. The Author(s).)
Competing Interests: Declarations. Ethical approval: All the animal experiments were carried out in accordance with the guidelines of the French Ministry of Research, and the protocols were approved by the Ethical Committees of the Region Nord Pas de Calais and the French Ministry of Research (agreement numbers APAFIS #20717-2019052015506229 and APAFIS #36244-2022031617542892). Competing interests: The authors declare no competing interests.
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Contributed Indexing: Keywords: Live attenuated vaccine; Mucosal immunity; Pertussis; SARS-CoV-2 nucleocapsid protein
Substance Nomenclature: 0 (Pertussis Vaccine)
0 (Vaccines, Attenuated)
0 (Coronavirus Nucleocapsid Proteins)
0 (Virulence Factors, Bordetella)
0 (Protein Subunit Vaccines)
0 (Immunoglobulin G)
63GD90PP8X (pertactin)
0 (Bacterial Outer Membrane Proteins)
Entry Date(s): Date Created: 20260529 Date Completed: 20260729 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13421274
DOI: 10.1007/s00253-026-13887-x
PMID: 42213183
Database: MEDLINE
Description
ISSN:1432-0614
DOI:10.1007/s00253-026-13887-x