Immunization of young heifers with staphylococcal immune evasion proteins before natural exposure to Staphylococcus aureus induces a humoral immune response in serum and milk

dc.contributor.authorBenedictus, Lindert
dc.contributor.authorRavesloot, Lars
dc.contributor.authorPoppe, Kim
dc.contributor.authorDaemen, Ineke
dc.contributor.authorBoerhout, Eveline
dc.contributor.authorVan Strijp, Jos
dc.contributor.authorBroere, Femke
dc.contributor.authorRutten, Victor P.M.G.
dc.contributor.authorKoets, Ad
dc.contributor.authorEisenberg, Susanne
dc.date.accessioned2020-07-17T06:21:21Z
dc.date.available2020-07-17T06:21:21Z
dc.date.issued2019-01-07
dc.descriptionAdditional file 1: Comparison of the immune responses against LukM in the intranasal immunization group between week 0 and 7. IgG1 and IgG2 LukM specific antibodies in serum. S/P = Sample to Positive ratio. NS = Not significant. Antibody levels between week 0 and 7 were compared using paired student’s T-test.en_ZA
dc.descriptionAdditional file 2: Comparison of the immune responses against LukM at week 7 between the four initial treatment groups. IgG1 (a) and IgG2 (b) LukM specific antibodies in serum. IFNg (c) and IL17 (d) production following stimulation of whole blood with LukM for 48 h and 72 h respectively. S/P = Sample to Positive ratio. NS = Not significant. Groups were compared using unpaired student’s T-test.en_ZA
dc.descriptionAdditional file 3: Sample dilutions for LukM, Efb and S. aureus wholecell specific IgG1 and IgG2 ELISAs.en_ZA
dc.descriptionAdditional file 4: Flow cytometry gating strategy.en_ZA
dc.descriptionAdditional file 5: Correlation of Staphylococcus aureus specific antibodies between colostrum and serum of dams at calving or calves one week after colostrum ingestion. IgG1 (a, c, e) and IgG2 (b, d, f) antibodies specific for whole SA bacterium (a, b), LukM (c, d) and EfB (e, f). Correlation between dam colostrum and dam and calf serum antibody levels was analyzed by linear regression. S/P = Sample to positive ratio.en_ZA
dc.descriptionAdditional file 6: Proliferation of gamma delta T-cells following stimulation with LukM and EfB. Proliferation was measured as the percentage of gamma delta T-cells with diluted CFSE following 96 h stimulation with LukM (a) or EfB (b). + = P < 0,05 before correction for multiple comparisons. * = P <0,05 after correction for multiple comparisons.en_ZA
dc.descriptionAdditional file 7: Intracellular cytokine expression of CD4 and CD8 Tcells following stimulation with LukM and EfB. Percentage of CD4 (a, b, e, f) or CD8 (c, d, g, h) T-cells positive for intracellur IFNg (a, b, c, d) or IL17a (e, f, g, h) following 6 day stimulation with LukM (a, c, e, g) or EfB (b, d, f, h). + = P < 0,05 before correction for multiple comparisons.en_ZA
dc.description.abstractBACKGROUND : Staphylococcus aureus, a leading cause of mastitis in dairy cattle, causes severe mastitis and/or chronic persistent infections with detrimental effects on the cows’ wellbeing, lifespan and milk production. Despite years of research there is no effective vaccine against S. aureus mastitis. Boosting of non-protective pre-existing immunity to S. aureus, induced by natural exposure to S. aureus, by vaccination may interfere with vaccine efficacy. The aim was to assess whether experimental immunization of S. aureus naïve animals results in an immune response that differs from immunity following natural exposure to S. aureus. RESULTS : First, to define the period during which calves are immunologically naïve for S. aureus, Efb, LukM, and whole-cell S. aureus specific serum antibodies were measured in a cohort of newborn calves by ELISA. Rising S. aureus specific antibodies indicated that from week 12 onward calves mounted an immune response to S. aureus due to natural exposure. Next, an experimental immunization trial was set up using 8-week-old heifer calves (n = 16), half of which were immunized with the immune evasion molecules Efb and LukM. Immunization was repeated after one year and before parturition and humoral and cellular immunity specific for Efb and LukM was determined throughout the study. Post-partum, antibody levels against LukM and EfB were significantly higher in serum, colostrum and milk in the experimentally immunized animals compared to animals naturally exposed to S. aureus. LukM specific IL17a responses were also significantly higher in the immunized cows post-partum. CONCLUSIONS : Experimental immunization with staphylococcal immune evasion molecules starting before natural exposure resulted in significantly higher antibody levels against Efb and LukM around parturition in serum as well as the site of infection, i.e. in colostrum and milk, compared to natural exposure to S. aureus. This study showed that it is practically feasible to vaccinate S. aureus naïve cattle and that experimental immunization induced a humoral immune response that differed from that after natural exposure only.en_ZA
dc.description.departmentVeterinary Tropical Diseasesen_ZA
dc.description.librarianam2020en_ZA
dc.description.sponsorshipThe Alternatives for Antibiotics (ALTANT) EVAC-2 project subsidized by the Ministry of Economic Affairs, Agriculture and Innovation of the Dutch government.en_ZA
dc.description.urihttps://bmcvetres.biomedcentral.comen_ZA
dc.identifier.citationBenedictus, L., Ravesloot, L., Poppe, K. et al. 2019, 'Immunization of young heifers with staphylococcal immune evasion proteins before natural exposure to Staphylococcus aureus induces a humoral immune response in serum and milk', BMC Veterinary Research, vol. 15, art. 15, pp. 1-13.en_ZA
dc.identifier.issn1746-6148 (online)
dc.identifier.other10.1186/s12917-018-1765-9
dc.identifier.urihttp://hdl.handle.net/2263/75338
dc.language.isoenen_ZA
dc.publisherBioMed Centralen_ZA
dc.rights© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.en_ZA
dc.subjectStaphylococcus aureusen_ZA
dc.subjectMastitisen_ZA
dc.subjectExperimental immunizationen_ZA
dc.subjectNatural exposureen_ZA
dc.subjectNon-protective immunityen_ZA
dc.subjectMilk antibodiesen_ZA
dc.subjectLukMen_ZA
dc.subjectEfben_ZA
dc.subjectCattleen_ZA
dc.subjectDairy cattleen_ZA
dc.titleImmunization of young heifers with staphylococcal immune evasion proteins before natural exposure to Staphylococcus aureus induces a humoral immune response in serum and milken_ZA
dc.typeArticleen_ZA

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