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Infect Immun. 2018 Sep 21;86(10). pii: e00857-17. doi: 10.1128/IAI.00857-17. Print 2018 Oct.

Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using a Bordetella pertussis Challenge Model in Mice.

Author information

1
Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, West Virginia, USA.
2
Vaccine Development Center at West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.
3
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
4
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
5
Department of Medicine, Section of Infectious Diseases, West Virginia University, Morgantown, West Virginia, USA.
6
Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, West Virginia, USA fdamron@hsc.wvu.edu.

Abstract

Bordetella pertussis is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine). Adenylate cyclase toxin (ACT) is a major virulence factor of B. pertussis that is (i) required for establishment of infection, (ii) an effective immunogen, and (iii) a protective antigen. The C-terminal repeats-in-toxin domain (RTX) of ACT is sufficient to induce production of toxin-neutralizing antibodies. In this study, we characterized the effectiveness of vaccines containing the RTX antigen against experimental murine infection with B. pertussis RTX was not protective as a single-antigen vaccine against B. pertussis challenge, and adding RTX to 1/5 human dose of aP did not enhance protection. Since the doses of aP used in murine studies are not proportionate to mouse/human body masses, we titrated the aP from 1/20 to 1/160 of the human dose. Mice receiving 1/80 human aP dose had bacterial burden comparable to those of naive controls. Adding RTX antigen to the 1/80 aP base resulted in enhanced bacterial clearance. Inclusion of RTX induced production of antibodies recognizing RTX, enhanced production of anti-pertussis toxin, decreased secretion of proinflammatory cytokines, such as interleukin-6, and decreased recruitment of total macrophages in the lung. This study shows that adding RTX antigen to an appropriate dose of aP can enhance protection against B. pertussis challenge in mice.

KEYWORDS:

Bordetella pertussis; DTaP; acellular pertussis vaccines; adenylate cyclase toxin; pertussis; vaccines; whooping cough

PMID:
30012638
PMCID:
PMC6204743
DOI:
10.1128/IAI.00857-17
[Indexed for MEDLINE]
Free PMC Article

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