NOVEL VACCINES TO PREVENT BOVINE MASTITIS CAUSED BY STAPHYLOCOCCUS AUREUS AND STREPTOCOCCUS UBERIS

Staphylococcus aureus and Streptococcus uberis are important bacterial agents of mastitis that can produce chronic subclinical disease in dairy cattle. Despite improved control measures and understanding of disease mechanisms over the past two decades, S. aureus and S. uberisremain leading agents of disease and cause considerable economic loss every year in the U.S. To circumvent the need for antibiotics and more effectively prevent disease, the ideal method of mastitis control is a vaccine. The delivery of vaccines by the mucosal route, or directly to the mammary gland, is highly desirable as a more effective and less costly alternative to needle injection. Cholera toxin (CT), produced by Vibrio cholerae, is a potent immunomodulator and mucosal vaccine adjuvant that can promote antigen uptake, stimulate humoral and cellular responses and reduce inflammation. Chimeric A2/B molecules comprise the native CT binding subunit and non-toxic A2 domain fused to a vaccine antigen. It is our objective to characterize the efficacy of these purified molecules as vaccines against S. aureus mastitis, and to construct additional A2/B chimeras to incorporte into a multivalent combination S.aureus and S. uberis vaccine. Specificialy, we propose to: 1) rigorously characterize immune responses stimulated by intranasal, intramammary and intravaginal administration of A2/B chimeras containing S. aureus IsdA and ClfA in cows, 2) utilitize genomic and proteomic analysis to identify conserved antigens for incorporation into A2/B chimeras and 3) evaluate the protective efficacy of IsdA-CTA2/B and ClfA-CTA2/B in a bovine model of staphylococcal mastitis. These studies represent essential steps toward the development of novel S. aureus and S. uberis vaccines that will circumvent needle-delivery. The long-term goals will have a significant impact on animal health and the economics of milk production in Idaho and the U.S.