Meeting the requirements for delayed release of oral vaccines for fish

While fish lack some of the specialized cellular and tissue components of the gut associated lymphoid tissues (GALT) of mammals, there is considerable evidence for the ability of the enterocytes, especially in the hind gut segment, to take up antigens and translocate them to macrophages and lymphocytes in the lamina propria and, under certain circumstances, to systemic lymphoid organs, i.e. kidney and spleen. Current evidence from carp suggests that oral delivery of antigens stimulates antibody production in the gut, gill and skin, but not in the kidney and blood, while parenteral injection of antigen stimulates the systemic compartment and not the mucosal compartment. However, in salmonids and the dab, evidence suggests that oral immunization stimulates only low responses in the gill, gut and skin, while injection stimulates both systematic and mucosal responses and stimulates the latter more effectively than oral immunization. Thus, while there is evidence of a common mucosal immune system in fish, there appears to be some species variation in the extent of its compartmentalization. There is also species variation in the nature of antigen uptake by the enterocytes. In carp, only soluble antigens are effectively taken up (by pinocytosis), while in salmonids, whole bacterial cells, as well as soluble antigens, can be taken up. Furthermore, exposure of antigen to conditions in the anterior gut, while not necessarily preventing uptake by hind gut enterocytes, may affect antigen translocation to the systemic compartment. Present information, while still very incomplete, indicates that orally delivered antigen must be protected from digestion and other forms of modification in the anterior intestine and delivered to the hind gut enterocytes in a form which can be taken up by these cells and translocated in a strongly immunogenic form to the systemic immune compartment. Some potentially useful methods of achieving this are reviewed.