RT Journal Article
SR Electronic
T1 IL-10 induced by alum-adjuvanted acellular pertussis vaccine reduces its capacity to induce protective respiratory tissue-resident CD4 T cells
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 253
DO 10.1183/23120541.LSC-2022.253
VO 8
IS suppl 8
A1 Caitlín Ní Chasaide
A1 Charlotte Leane
A1 Alicja Misiak
A1 Lisa Borkner
A1 Lucy Curham
A1 Pauline Schmitt
A1 Mieszko M. Wilk
A1 Kingston H. G. Mills
YR 2022
UL http://openres.ersjournals.com/content/8/suppl_8/253.abstract
AB Whooping cough (pertussis) remains a global health problem despite widespread vaccination. Infection with Bordetella pertussis induces tissue-resident memory CD4 T cells (TRM) with Th1/Th17 phenotype, which confer protective immunity against re-infection. Current alum-adjuvanted acellular pertussis (aP) vaccines (aP/alum) protect against lung infection but induce limited cellular immunity or expansion of respiratory TRM cells and fail to prevent infection of the nasal mucosa or bacterial transmission. This study aims to elucidate the mechanisms by which aP/alum vaccines fail to recruit TRM cells to the nasal tissue and how novel adjuvants may overcome this deficit. Immunization of mice with aP/alum vaccine induced antibody responses but failed to induce systemic Th1 or Th17 responses and TRM cells in nasal tissue after B. pertussis challenge. In contrast, immunization of mice with aP/alum vaccine induced IL-10 production in draining lymph nodes. Immunization of IL-10-deficient mice with an aP/alum vaccine promoted induction of respiratory IFN-γ and IL-17-secreting TRM cells and conferred protection against B. pertussis infection of the nasal cavity. Substitution or adding a novel adjuvant LP-GMP, comprising TLR2 and STING agonists, to an aP vaccine generated respiratory TRM cells and promoted bacterial clearance from the nasal mucosa. These findings suggest that IL-10 may play a role in the failure of aP/alum vaccines to protect against B. pertussis infection of the nasal mucosa by suppressing activation and recruitment of TRM cells, but this can be overcome by adding the potent adjuvant LP-GMP to the aP/alum vaccine formulation.FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 253.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).