Staphylococcus aureus-Cholera Toxin Fusions as Novel Vaccines to Prevent Bovine Mastitis
Background: Mastitis represents the most common and costly disease affecting dairy cattle in the U.S. Developing a vaccine to prevent this disease would significantly improve animal health and reduce dependence on antibiotics. The S. aureus iron-regulated adhesin, IsdA, is a conserved adhesin that has shown promise as a vaccine candidate in animal models. Methods: Non-toxic chimeric fusions were constructed using IsdA and the cholera toxin A2 and B subunits (IsdA-CTA2/B). We have previously reported the ability of IsdA-CTA2/B to stimulate antigen-specific IgG and IgA after mucosal delivery in mice. 150 g of purified IsdA-CTA2/B or IsdA alone was delivered intranasally to cows to characterize the immunogenicity of IsdA-CTA2/B as a potential vaccine against bovine mastitis. The success of the IsdA-CTA2/B fusion was assayed using IsdA-specific enzyme-linked immunosorbent assay (ELISA) on serum, milk, and nasal wash samples collected from immunized cows. In addition, we cloned the S. aureus clfA gene into a vector for ClfA-CTA2/B chimera expression. Results: IsdA-CTA2/B stimulates antigen-specific responses in cows that are higher than IsdA alone, however, further studies are needed and a multivalent vaccine that includes the ClfA antigen will likely promote stronger immune responses to prevent S. aureus infection.