Immunogenicity of a Staphylococcus aureus-Cholera Toxin A₂/B Vaccine for Bovine Mastitis

Authors

N. Misra, Boise State University
T. F. Wines, Boise State University
C. L. Knopp, Boise State University
R. Hermann, Boise State University
L. Bond, Boise State UniversityFollow
J. K. Tinker, Boise State UniversityFollow

Document Type

Article

Publication Date

6-7-2018

DOI

http://dx.doi.org/10.1016/j.vaccine.2018.04.067

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.

Comments

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Publication Information

Misra, N.; Wines, T. F.; Knopp, C. L.; Hermann, R.; Bond, L.; and Tinker, J. K.. (2018). "Immunogenicity of a Staphylococcus aureus-Cholera Toxin A₂/B Vaccine for Bovine Mastitis". Vaccine, 36(24), 3513-3521.