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.

• Authors: Annabelle Lim, Jowin K W Ng, Camille Locht, Sylvie Alonso
• Journal: Microbes and infection (Microbes Infect) Vol. 16 Issue 1 Pg. 51-60 (Jan 2014) ISSN: 1769-714X [Electronic] France
• PMID: 24140230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Antibodies, Bacterial
• Cytokines
• Pertussis Vaccine
• Vaccines, Attenuated
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (genetics)
• Animals
• Antibodies, Bacterial (immunology)
• Bordetella pertussis (enzymology, genetics, immunology)
• Cell Line
• Cytokines (biosynthesis)
• Gene Deletion
• Gene Order
• Humans
• Lung (immunology, microbiology)
• Mice
• Pertussis Vaccine (genetics, immunology)
• Phenotype
• Vaccines, Attenuated (genetics, immunology)
• Whooping Cough (immunology, prevention & control)