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

Background: 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.</p

MOESM3 of The antibody response in the bovine mammary gland is influenced by the adjuvant and the site of subcutaneous vaccination

Additional file 3. Differences in least square means (Log 2 ) of Îą-toxin specific antibody isotype titers and neutralization titers

Sex differences in prevalence and outcomes of the different endotypes of chronic coronary syndrome in symptomatic patients undergoing invasive coronary angiography: Insights from the global ILIAS invasive coronary physiology registry

Background and aims: The management of chronic coronary syndrome (CCS) is informed by studies predominantly including men. This study investigated the relationship between patients sex and different endotypes of CCS, including sex-specific clinical outcomes. Methods: In patients with CCS undergoing coronary angiography, invasive Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) were measured. Patients were stratified into groups: 1) obstructive coronary artery disease (oCAD) (FFR≤0.80, no revascularization), 2) undergoing revascularization, 3) non-obstructive coronary artery disease with coronary microvascular dysfunction (CMD) (FFR>0.80, CFR≤2.5), and 4) non-obstructive coronary artery disease without CMD (FFR>0.80 and CFR>2.5). Results: 1836 patients (2335 vessels) were included, comprising 1359 (74.0%) men and 477 (26.0%) women. oCAD was present in 14.1% and was significantly less prevalent in women than in men (10.3% vs 15.5%, respectively p < 0.01). Revascularization was present in 30.9% and was similarly prevalent in women and men (28.2% vs. 31.9%, respectively p = 0.13). CMD was present in 24.2% and was significantly more prevalent in women than men (28.6% vs 22.6%, respectively p < 0.01). Normal invasive measurements were found in 564 patients (33.0% women vs 30.0% men, p = 0.23). Male sex was associated with an increased risk of target vessel failure compared to women (HR.1.89, 95% CI 1.12–3.18, p = 0.018), regardless of CCS-endotype. Conclusions: Sex differences exist in the prevalence and outcomes of different endotypes of CCS in symptomatic patients undergoing invasive coronary angiography. In particular, oCAD (and subsequent revascularization) were more prevalent in men. Conversely, CMD was more prevalent in women. Overall, men experienced a worse cardiovascular outcome compared to women, independent of any specific CCS endotype.  </p