Immunogenicity of a Staphylococcus aureus-cholera toxin A2/B vaccine for bovine mastitis

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 A/B chimeras (IsdA-CTA/B and ClfA-CTA/B). Cows were intranasally inoculated with IsdA-CTA/B + ClfA-CTA/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 CTA/B chimeras to protect cows from mastitis caused by S. aureus.

Vaccination with a live-attenuated small-colony variant improves the humoral and cell-mediated responses against Staphylococcus aureus

“…Because of its effect on neutrophil activity, an improved Th17 response could represent an interesting way of enhancing phagocytic activity in the mammary gland, since neutrophils represent the dominant defense in the udder against mastitis-causing pathogens [31]. A recent bovine mastitis vaccination study using intranasal inoculation of cows with purified IsdA and ClfA-cholera toxin A2/B chimeras was attempted in order to stimulate mucosal immunity of the mammary gland [43]. The vaccine induced IL-4 expression but not IFN-γ or IL-17 in peripheral blood mononuclear cells of cows 60 days after the trial.…”

Organic Selenium Ameliorates Staphylococcus aureus-Induced Mastitis in Rats by Inhibiting the Activation of NF-κB and MAPK Signaling Pathways

“…Selenium is necessary to maintain excellent reproductive performances in dairy cattle due to its beneficial biochemical and pharmacological properties ( 14 , 15 ). And Se supplementation showed protective effects on the mammary gland health, which decreased the somatic cells count and incidence rate of the mastitis ( 16 ). SeHLan is a new selenoamino acid discovered in selenized Japanese pungent radish ( 17 ).…”

Evaluation of the Efficacy of a Cholera Toxin-Based Staphylococcus aureus Vaccine against Bovine Intramammary Challenge

“…As reported previously, we have incorporated S. aureus IsdA and ClfA into a CTA 2 /B vaccine platform (IsdA + ClfA-CTA 2 /B). After two intranasal doses this vaccine was found to stimulate significant S. aureus antigen-specific humoral and cellular immunity in bovine blood and milk [ 49 ].…”