Tolerance or response following intestinal exposure to antigen

 

Oral vaccines provide a major means to vaccinate large populations at a low cost. This approach is of particular interest to the poultry industry in which major vaccination programs include the inoculation of individual chicks in flocks containing over 100,000 birds. One of the main issues in the development of intestinal vaccines is to be able to predict the immunogenicity and consequential protection of the designed vaccine. The immunological properties of a vaccine depend on the structure of the vaccine itself and on the interaction between the immunogen and the intestinal immune system. A given protein antigen can be either immunogenic or tolerogenic depending on the circumstances it is encountered by the immune system. Thus, protein antigens administered orally can frequently induce immune tolerance (oral tolerance), while if administered by parenteral injection – they will induce robust immune responses. Hence, with the aim of developing potent oral-vaccination strategies, we are interested in investigating mechanisms responsible for oral tolerance, and in developing strategies for oral immunization - and particularly so in poultry. Again, the entire research program focused on the quest to develop efficient oral vaccines for poultry.

Several of our major findings are:

• We were the first to publish that clonal anergy is a mechanism for oral tolerance.

• Oral tolerance can be demonstrated for both Th1 and Th2 phenotypes.

• The co-stimulatory molecule CTLA-4 is involved in generation of peripheral tolerance.

• Birds are surprisingly different from mammals in that oral antigen usually leads to response rather than tolerance.

• Oral tolerance may be induced in very young chicks with immature intestinal systems.

 

Key Publication: Klipper, E., Sklan, D. & Friedman, A. (2004). Maternal antibodies block induction of oral tolerance in newly hatched chicks. Vaccine 22: 493-502.