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Title: Protective role of adenylate cyclase in the context of a live pertussis vaccine candidate
Authors: Lim, A. 
Ng, J.K.W.
Locht, C.
Alonso, S. 
Keywords: Adenylate cyclase
Bordetella pertussis
Issue Date: Jan-2014
Citation: Lim, A., Ng, J.K.W., Locht, C., Alonso, S. (2014-01). Protective role of adenylate cyclase in the context of a live pertussis vaccine candidate. Microbes and Infection 16 (1) : 51-60. ScholarBank@NUS Repository.
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. Invivo, whereas the protective efficacy of the CyaA-deficient mutant was comparable to the parental strain at a vaccine dose of 5×105colony forming units (CFU), it was significantly impaired at a vaccine dose of 5×103CFU. 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. © 2013 Institut Pasteur.
Source Title: Microbes and Infection
ISSN: 12864579
DOI: 10.1016/j.micinf.2013.10.002
Appears in Collections:Staff Publications

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