Vaccination: tipping the balance from pathogen to host.

The aim of this thesis is to find strategies to develop vaccines for protection against pathogens that do not induce adequate protective immunity after natural infection or after vaccination with the infectious agent. To reach this objective, three main areas needed to be controlled: 1) detailed monitoring of antigen specific responses by both B cells and T cells, and the resulting antibodies, 2) measuring qualitative and quantitative variations in the induction method by using antigens of reduced complexity. Only when the specificity is under full control, comparisons can be made, 3) stimuli to modulate the nature of a response independent of specificity. These three areas form the main subjects of the different chapters in this thesis. The authors have focussed on the chicken to study effects of vaccine composition on the immunological response. Studies in livestock and companion animals have additional value compared to common experimental animals, because they are both the experimental and the target species at the same time. As in mammals, respiratory infections in poultry are an important cause of disease. Infectious Bronchitis Virus and Escherichia coli were the pathogens of choice to study vaccine strategies in this thesis. In this thesis, the development of an ELISPOT and intracellular staining assay are described as novel tools to examine T cell responses in the chicken. Using these tools, the phenomenon of polyclonal stimulation of chicken immune cells by IBV has been investigated. We also examined DNA immunization as a vaccine strategy to protect chickens against IBV. To gain insight into the effects of immune modulation on inflammatory responses, enhanced susceptibility of broilers to Escherichia coli infection after exposure to IBV was studied. The results presented in this thesis provide useful insights into host-pathogen interactions and the immunological processes behind vaccination. It is hoped that these news insights can contribute to the development of improved vaccines and vaccination strategies.