Protective role of adenylate cyclase in the context of a live pertussis vaccine candidate.

Abstract:

:Despite high vaccination coverage, pertussis remains an important respiratory infectious disease and the least-controlled vaccine-preventable infectious disease in children. Natural infection with Bordetella pertussis is known to induce strong and long-lasting immunity that wanes later than vaccine-mediated immunity. Therefore, a live attenuated B. pertussis vaccine, named BPZE1, has been developed and has recently completed a phase I clinical trial in adult human volunteers. In this study, we investigated the contribution of adenylate cyclase (CyaA) in BPZE1-mediated protection against pertussis. A CyaA-deficient BPZE1 mutant was thus constructed. Absence of CyaA did not compromise the adherence properties of the bacteria onto mammalian cells. However, the CyaA-deficient mutant displayed a slight impairment in the ability to survive within macrophages compared to the parental BPZE1 strain. In vivo, whereas the protective efficacy of the CyaA-deficient mutant was comparable to the parental strain at a vaccine dose of 5 × 10(5) colony forming units (CFU), it was significantly impaired at a vaccine dose of 5 × 10(3) CFU. This impairment correlated with impaired lung colonization ability, and impaired IFN-γ production in the animal immunized with the CyaA-deficient BPZE1 mutant while the pertussis-specific antibody profile and Th17 response were comparable to those observed in BPZE1-immunized mice. Our findings thus support a role of CyaA in BPZE1-mediated protection through induction of cellular mediated immunity.

journal_name

Microbes Infect

journal_title

Microbes and infection

authors

Lim A,Ng JK,Locht C,Alonso S

doi

10.1016/j.micinf.2013.10.002

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

51-60

issue

1

eissn

1286-4579

issn

1769-714X

pii

S1286-4579(13)00194-9

journal_volume

16

pub_type

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