Polyvalent vaccines in fish: the interactive effects of multiple antigens

Fermentation and cell-grown products commonly used as fish vaccines present a relatively crude mixture of antigenic and other immunologically active components to the immune system. The specific antigenic make-up and the potential protective immunogenicity of this mixture is dependent upon the strain of the pathogen, production parameters, inactivation methods, down-stream processing, product formulation, storage conditions and the delivery method under which the final product is applied. In the past ten years, commercial vaccine products for fish have more often consisted of mixtures of multiple products, including two, three, four and five vaccines. Such mixtures present an even more extensive and complex array of antigens to the immune system. Considering the fact that not all antigens stimulate a protective immune response, that antigens vary in their immuno-dominance relative to each other and that the immune system of fish has a defined and limited capacity to respond to individual antigenic substances, it becomes increasingly difficult to formulate these complex mixtures into safe and effective commercial products. The clonal capacity of fish to respond to multiple antigens may depend on a variety of factors including host species and age, water temperature, route of administration and temporal considerations. There is growing evidence that antigenic as well as non-antigenic components of vaccines can interact synergistically or antagonistically and that they can stimulate, cross-react with, inhibit or even suppress the immune response to specific antigens. This paper reviews current knowledge about the interactive effects of antigenic components of fish vaccines and gives specific examples of how these interactions might affect the formulation and performance of multivalent products. This paper also considers the potential basis for these interactive effects and discusses technical approaches that take advantage of this knowledge for the development of new multivalent products.