Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine.

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Ross PJ, Sutton CE, Higgins S, Allen AC, Walsh K, Misiak A, Lavelle EC, McLoughlin RM, Mills KH, Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine., PLoS pathogens, 9, 4, 2013, e1003264Download Item:

Abstract:
Whooping cough caused by
Bordetella pertussis
is a re-emerging infectious disease despite the introduction of safer acellular
pertussis vaccines (Pa). One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis
vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be
associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host
protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the
relative contribution of Th1 and Th17 cells in host immunity to infection with
B. pertussis
and in immunity induced by
immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings
demonstrate that Th1 and Th17 both function in protective immunity induced by infection with
B. pertussis
or immunization
with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak
Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa
and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully
protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective
immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell
recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by
substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective
immunity through IL-1
b
-induced IL-17A production, but also reveal that optimum protection against
B. pertussis
requires
induction of Th1, but not Th2 cells
Sponsor
Grant Number
Science Foundation Ireland (SFI)
11/PI/1036
Author's Homepage:
http://people.tcd.ie/mclougrmhttp://people.tcd.ie/casutton
http://people.tcd.ie/millsk
http://people.tcd.ie/lavellee
Description:
PUBLISHED
Author: MCLOUGHLIN, RACHEL; LAVELLE, EDWARD; MILLS, KINGSTON; SUTTON, CAROLINE; HIGGINS, SARAH; ALLEN, AIDEEN
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PLoS pathogens9
4
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Full text availableKeywords:
Bordetella pertussis, whooping coughSubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1371/journal.ppat.1003264Licences: