Immunization with whole cell but not acellular pertussis vaccines primes CD4 T_RM cells that sustain protective immunity against nasal colonization with Bordetella pertussis

ABSTRACT

Protective immunity wanes rapidly after immunization of children with acellular pertussis (aP) vaccines and these vaccines do not prevent nasal colonization or transmission of Bordetella pertussis in baboons. In this study, we examined the role of tissue-resident memory T (T_RM) cells in persistent protective immunity induced by infection or immunization with aP and whole-cell pertussis (wP) vaccines in mice. Immunization of mice with a wP vaccine protected against lung and nasal colonization, whereas an aP vaccine failed to protect in the nose. IL-17 and IFN-γ-secreting CD69⁺CD4⁺ T_RM cells were expanded in the lung and nasal tissue after B. pertussis challenge of mice immunized with wP, but not aP vaccines. However, previous infection induced the most persistent protection against nasal colonization and this correlated with potent induction of nasal tissue T_RM cells, especially IL-17-secreting T_RM cells. Blocking T cell migration to respiratory tissue during immunization with a wP vaccine impaired bacterial clearance, whereas transfer of T_RM cells from convalescent or wP-immunized mice conferred protection to naïve mice. Our findings reveal that previous infection or wP vaccination are significantly more effective than aP vaccination in conferring persistent protective immunity against B. pertussis and that this is mediated by respiratory T_RM cells.

KEYWORDS:

• Bordetella pertussis
• pertussis vaccine
• tissue-resident memory T cell
• Th1 and Th17 cells

Acknowledgements

We thank Barry Moran for assistance with flow cytometry and cell sorting.

Disclosure statement

KHG Mills is an inventor on a patent that protects lipoproteins from B. pertussis as potential antigens and adjuvants for a next generation pertussis vaccine.

Author contributions

K.H.G.M. planned the project, designed experiments, analysed and interpreted data. M.M.W. and L.B. designed and performed experiments and analysed data. A.M., L.C and A.C.A. assisted with in vivo experiments. M.M.W and K.H.G.M. wrote the manuscript. All authors reviewed the manuscript.

Additional information

Funding

This work was supported by research grants from Science Foundation Ireland [16/IA/4468; 12/RI/2340-7] and by the PERISCOPE project, which has received funding from the Innovative Medicines Initiative 2 Joint undertaking under grant agreement No 115910. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and European Federation of Pharmaceutical Industries and Associations and Bill and Melinda Gates Foundation.