학술논문
Development and characterisation of a novel vaccine for Bordetella pertussis (whooping cough)
Document Type
Electronic Thesis or Dissertation
Author
Source
Subject
Language
English
Abstract
Bordetella pertussis is the causative agent of pertussis (whooping cough) which is a respiratory infection, particularly dangerous for babies and young infants. Protection against pertussis relies on the induction of potent T-cell and antibody responses. Current acellular pertussis (aP) vaccines induce strong antibody responses and T-cell helper type 2 (Th2) response but are less effective at producing Th1-type immunity necessary for complete and fast bacterial clearance. Although, aP vaccines protect against severe disease, the vaccine-induced protection wanes over time, and despite high aP vaccination coverage in many developed countries, pertussis is a re-emerging disease. In this thesis, I explored the use of replication-deficient adenovirus (Ad) and modified vaccinia virus Ankara (MVA) vectors as platforms for development of novel pertussis vaccines. Pertussis toxin (PT), fimbriae adhesins (Fim2, Fim3 and FimD), iron-binding proteins (IRP1-3 and AfuA) and adenylate cyclase toxin (ACT) were selected as vaccine candidate antigens. Our aim was to enhance Th1-type responses against B. pertussis and induce strong antigen-specific and neutralising antibodies that prevent lung (and nasal) colonisation of B. pertussis. I therefore evaluated the vaccines' different immunisation regimens and their potential to mediate such immune responses in mice. A single intramuscular immunisation with a number of the Ad vaccines induced partial protection in mice. These constructs encoded the full length of the catalytic S1-235 subunit of PT, Fim3, AC and RTX domains of ACT. In particular, the Ad RTX vaccine may have the potential to prevent pertussis infection as 60% of mice immunised with one dose of the vaccine were fully protected against lung infection. In addition, the Ad S1-235 vaccine generated a PT-specific Th1-type response. The results indicate the potential of viral vectored vaccines to prevent pertussis infection either on their own or as future studies may reveal, using them in combination with different types of pertussis vaccines.