A number of problems are uniquely associated with vaccination of dairy cows for mastitis. One of these is that the number of mastitis pathogens is numerous and heterogeneous. Vaccine efforts have concentrated mainly on the major mastitis pathogens. While at least one S. aureus bacterin has been commercially available for a number of years, no large-scale, independent field trials have been published in refereed journals which support the efficacy of this vaccine. Experimental vaccines for S. aureus composed of pseudocapsule-enriched bacterins supplemented with alpha- and/or beta-toxoids appear promising, but none of these has been commercialized. With S. uberis, some protection against homologous strain challenges was reported recently with a live strain and a bacterin, but other data from the same laboratory showed this vaccine would not protect against heterologous challenge strains. At this time there is only one highly effective vaccine for mastitis, the core-antigen vaccine for coliform mastitis. All of the commercially available vaccines for this indication are bacterins of rough mutants of E. coli strain J5 or Salmonella spp. Preliminary success with an experimental vaccine based on the plasminogen activator of S. uberis is a very different approach for a mastitis vaccine. Little success has been reported with vaccination against other mastitis pathogens. For diagnostic methods, the high somatic cell count, as measured by direct count or indirect assays, remains the cornerstone of mastitis diagnosis. However, for subclinical mastitis, bacterial cell culture is a reliable diagnostic method. Pathogen identification may rely on older biochemical testing methods or newer commercial identification systems, depending on the laboratory budget. ELISA assays also have been used to assess herd infection status. Epidemiologic studies have used DNA fingerprinting and ribotyping, but none of these methods has yet produced an easily utilized commercial format. Within the next decade, additional efficacious vaccines for several of the most common agents for bovine mastitis are likely. A review written at that time then can be more fact than fiction.
The poultry industry constitutes a significant sector of world agriculture. In the United States, more than 8 billion birds are produced yearly with a value exceeding $20 billion. Broiler chickens are the largest segment of the industry. Birds raised under commercial conditions are vulnerable to environmental exposure to a number of pathogens. Therefore, disease prevention by vaccination is an integral part of flock health management protocols. Active immunization using live vaccines is the current industry standard. Routinely used vaccines in chickens include MDV, NDV, IBV, and IBDV, and in turkeys NDV and HEV. Newer vaccines, including molecular recombinants in which genes of immunogenic proteins from infectious agents are inserted into a live viral vector, are also being examined for commercial use. Efforts are under way to enhance vaccine efficacy by the use of adjuvants, particularly cytokines. The vaccine delivery systems include in ovo injection, aerosol, spray, drinking water, eye drop, and wing web injection. The in ovo vaccination procedure is relatively new and at the present time it is used primarily to vaccinate broiler chickens against MDV. Birds respond to vaccines by developing humoral and cellular immune responses. Bursa of Fabricius and the thymus serve as the primary lymphoid organs of the immune system. B cells use surface immunoglobulins as antigen receptors and differentiate into plasma cells to secrete antibodies. Three classes of antibodies are produced: IgM, IgG (also called IgY), and IgA. Successful vaccinal response in a flock is often monitored by demonstrating a rise in antibody titer within a few days of vaccination. ELISA is used most commonly for serologic monitoring. T cells are the principal effector cells of specific cellular immunity. T cells differentiate into alpha beta and gamma delta cells. In adult birds, gamma delta cells may constitute up to 50% of the circulating T cells. Functionally, CD4+ cells serve as helper cells and CD8+ cells as cytotoxic/suppressor cells.
The present study showed that E. ictaluri RE-33 vaccine does not cause ESC but does stimulate protective immunity. The RE-33 vaccinates were protected against ESC for at least 4 months following a single bath immersion in a low number of E. ictaluri RE-33 without booster vaccination. Antibody responses are weak after RE-33 vaccination. Edwardsiella ictaluri RE-33 vaccine presents no risk or hazard to catfish. RE-33 vaccine will prevent ESC caused by most isolates of E. ictaluri in catfish. We recently obtained from USDA, Animal Plant Health Inspection Service (APHIS), and the state veterinarians of Alabama and Mississippi, approval to field test the RE-33 vaccine in young catfish. About 2-3 million 10- to 30-day-old channel catfish in Alabama and Mississippi have been vaccinated since June 1997 with no adverse effects of vaccination.
The licensing procedures reviewed above provide a framework for the production of pure, safe, potent, and efficacious veterinary biological products. The licensing, inspection, and testing activities of the Veterinary Biologics program provide the oversight necessary to ensure the continued availability of high-quality veterinary biological products in the United States.
Delivery of protein antigens to the GALT can result in immunity or oral tolerance depending on the circumstances of the encounter. One mechanism by which mucosal adjuvants can affect these circumstances is by the induction of macrophage cytokines, including IL-1 and IL-12. These cytokines can directly affect the immune response by their effects on antigen-specific T cells and by the induction of IFN-gamma by T cells or NK cells. This IFN-gamma also activates macrophages to up-regulate MHC or costimulatory molecules and by further inducing IL-1 and IL-12. In effect, mucosal adjuvants function both directly and indirectly as activators of antigen presenting cells, resulting in stimulation of the immune response to coincidental antigens. Our studies in swine have shown CT is a potent mucosal adjuvant for CT-B. CT also increased IL-1 and IL-12 mRNA in cultured macrophages, especially after activation with IFN-gamma. The effect of CT on the secretion of bioactive IL-12 protein is currently being investigated. While the mucosal adjuvanticity of CT involves a variety of mechanisms, these findings suggest a role for the induction of the macrophage cytokines IL-1 and IL-12.
During the last 10 years, investigation of the bovine immune system has generated knowledge and reagents that can now be applied to study the mechanisms of immunity to disease and the identity of antigens recognized by protective immune responses. Such studies can indicate which antigens are likely to be effective in subunit vaccines and also highlight the type of antigen delivery system that will be required for a vaccine to induce a protective immune response. In the case of bovine RSV, studies of immune responses in the target host have demonstrated that both antibody and CTL responses play an important role in immunity. Both the F and G glycoproteins have been identified as targets of protective antibodies, and systems have been established that will allow the identification of the viral antigens recognized by CTL. Further studies of CD4+ T-cell responses to the virus are required to determine whether or not components of the response have the potential to enhance disease and, therefore, need to be avoided in vaccination strategies.