Immunogenicity of a Staphylococcus aureus-cholera toxin A2/B vaccine for bovine mastitis. Issue 24 (7th June 2018)

• Record Type: Journal Article
• Authors: Misra, N.; Wines, T.F.; Knopp, C.L.; Hermann, R.; Bond, L.; Mitchell, B.; McGuire, M.A.; Tinker, J.K.
• Is Part Of: Vaccine. Volume 36:Issue 24(2018)
• Page Start: 3513
• Page End: 3521
• Publication Date: 2018-06-07
• Subjects: Staphylococcus -- Vaccine -- Bovine -- Mastitis; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.04.067
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: Staphylococcus aureus causes a chronic, contagious disease of the udder, or mastitis, in dairy cows . This infection is often refractory to antibiotic treatment, and has a significant economic impact on milk production worldwide . An effective vaccine to prevent S. aureus mastitis would improve animal health, reduce antibiotic dependence and inform human vaccine approaches. The iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) are conserved S. aureus extracellular-matrix adhesins and target vaccine antigens. Here we report the results of two bovine immunogenicity trials using purified IsdA and ClfA-cholera toxin A2 /B chimeras (IsdA-CTA2 /B and ClfA-CTA2 /B). Cows were intranasally inoculated with IsdA-CTA2 /B + ClfA-CTA2 /B at dry off and followed for 70 days. Trial 1 utilized three groups with one or two booster doses at a total concentration of 600 or 900 μg. Trial 2 utilized two groups with one booster at a total concentration of 1200 μg. Humoral immune responses in serum and milk were examined by ELISA. Responses in serum were significant between groups and provide evidence of antigen-specific IgG induction after vaccination in both trials. Cellular proliferation was detected by flow cytometry using antigen-stimulated PBMCs from day 60 of Trial 2 and revealed an increase in CD4+ T cells from vaccinated cows. IsdA and ClfA stimulation induced IL-4 expression, but not IFN-γ or IL-17, in PBMCs from day 60 as determined by cytokine expression analysis. Opsonophagocytosis of S. aureus confirmed the functional in vitro activity of anti-IsdA antibodies from Trial 2 serum and milk. The vaccine was well tolerated and safe, and results support the potential of mucosally-delivered CTA2 /B chimeras to protect cows from mastitis caused by S. aureus .