Nature Microbiology | Respiratory delivery of antibiotic-inactivated Bordetella pertussis vaccine induces T cell-mediated immune protection

This study developed a novel antibiotic-inactivated Bordetella pertussis vaccine (AIBP) delivered via the respiratory route. It effectively induces TH17 and TH1-type CD4 tissue-resident memory T cells and IgA antibodies, significantly enhancing immune protection against nasal and pulmonary infections without inducing notable systemic inflammatory responses. This work provides a new and effective strategy for the development of pertussis vaccines.

 

Literature Overview
This article, 'Respiratory immunization using antibiotic-inactivated Bordetella pertussis confers T cell-mediated protection against nasal infection in mice', published in Nature Microbiology, reviews the limitations of current acellular pertussis vaccines (aP) in inducing mucosal immunity and tissue-resident memory T cells (TRM), highlighting the necessity for developing novel respiratory vaccines. The study successfully induced effective immune responses using antibiotic-inactivated B. pertussis delivered via the respiratory route, demonstrating superior protection against nasal and pulmonary infections in mouse models.

Background Knowledge
Pertussis is an acute respiratory infectious disease caused by Bordetella pertussis, particularly affecting infants and young children with high morbidity and mortality. Despite high vaccination coverage, pertussis has been resurging. Current acellular pertussis vaccines (aP) can effectively prevent severe pulmonary infections but fail to induce nasal mucosal immunity, thus not blocking pathogen colonization and transmission. Traditional whole-cell vaccines (wP), while inducing stronger systemic immune responses, are administered via systemic routes (e.g., intramuscular injection) and cannot efficiently generate tissue-resident memory T cells (TRM) or secretory IgA, which are critical for mucosal immune defense. This study introduces a new vaccine strategy using antibiotic (e.g., ciprofloxacin) inactivated B. pertussis delivered via the respiratory route, effectively activating antigen-presenting cells and inducing TRM and IgA for strong nasal and pulmonary protection. The method was validated in mouse models for safety and efficacy and compared with existing vaccines, showing superior induction of mucosal immunity and TRM.

 

 

Research Methods and Experiments
The research team treated Bordetella pertussis strains with ciprofloxacin or levofloxacin, then delivered the inactivated vaccine (AIBP) via the respiratory route to mice. The colonization capacity of AIBP in the lung and nasal passages, systemic inflammatory responses, activation of antigen-presenting cells, TH1 and TH17 T cell responses, and production of IgA and IgG antibodies were evaluated. Additionally, the immunogenicity of AIBP in mice previously vaccinated with aP was assessed and compared with traditional whole-cell vaccines (wP).

Key Conclusions and Perspectives

• AIBP vaccine delivered via the respiratory route significantly activates B. pertussis-specific IL-17 and IFNγ-secreting CD4 TRM cells in the lung and nasal passages, whereas traditional aP vaccines do not.
• A single dose of AIBP vaccine induces effective IgA antibody responses, which are further enhanced after a second dose, while aP vaccines only induce IgG1 and IgG2c without significant IgA production.
• In terms of inactivation method, ciprofloxacin-treated B. pertussis preserves intact membrane structures, which is more favorable for antigen-presenting cell activation and induction of TH17 responses compared to formalin-treated wP vaccines.
• Mice immunized with AIBP completely cleared infections in both lung and nasal tissues after B. pertussis challenge, while aP vaccines offered only limited protection, particularly against nasal colonization.
• This protective effect is dependent on CD4 T cells and IL-17 signaling, as vaccination failed to confer protection in mice treated with anti-CD4 or anti-IL-17 antibodies.
• AIBP vaccine demonstrates superior safety compared to traditional wP vaccines. It does not induce systemic inflammatory cytokines such as IL-1β, TNF, or CRP after respiratory delivery, nor does it lead to the release of toxin proteins like PT.
• Mice previously vaccinated with aP still effectively responded to AIBP, indicating its potential as a booster immunization strategy even in the presence of a TH2-skewed immune background.

Research Significance and Prospects
This study introduces a new platform for developing safe and effective respiratory vaccines, particularly relevant for combating respiratory pathogens such as Bordetella pertussis. Since AIBP can induce mucosal immunity and tissue-resident T cells, it holds promise for reducing nasal colonization and transmission of pathogens, thereby contributing to herd immunity. Future research may further optimize the application of this vaccine in humans, explore its utility against other respiratory pathogens, and assess its immunogenicity in populations with diverse genetic backgrounds.

 

 

Conclusion
This study presents a novel respiratory vaccine platform, AIBP, based on antibiotic-inactivated Bordetella pertussis. By inducing IL-17 and IFNγ-secreting CD4 TRM cells and IgA antibodies, it significantly enhances immune protection against nasal and pulmonary infections in mice. The vaccine outperforms existing pertussis vaccines in terms of safety, immunogenicity, and protective efficacy, particularly in inducing mucosal immunity and long-term protection. As it is delivered via the respiratory route, does not rely on live bacteria, and does not trigger systemic inflammation, AIBP holds broad clinical translational potential. This achievement provides both a theoretical basis and technical approach for the development of novel vaccines against pertussis and other respiratory pathogens, while also offering new insights into mucosal immunology and vaccine delivery system design.

 

Seyed Davoud Jazayeri, Lisa Borkner, Caroline E Sutton, and Kingston H G Mills. Respiratory immunization using antibiotic-inactivated Bordetella pertussis confers T cell-mediated protection against nasal infection in mice. Nature Microbiology.