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.
Additional 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.
Additional 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.
Additional file 3: Sample dilutions for LukM, Efb and S. aureus wholecell
specific IgG1 and IgG2 ELISAs.
Additional 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.
Additional 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.
Additional 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.
In general antibiotics interact cooperatively with host defences, weakening and decreasing the virulence of microbial pathogens, thereby increasing vulnerability to phagocytosis and eradication by the intrinsic antimicrobial ...
BACKGROUND : Despite high levels of naturally-acquired immunity (NAI) within local communities in malaria high
transmission settings in Africa, such people often experience clinical disease during peak transmission months ...
Bipath, Priyesh; Levay, Peter F.; Olorunju, Steve; Viljoen, Margaretha(Makerere University Medical School, 2015-06)
BACKGROUND : A general non-specific marker of disease activity that could alert the clinician and prompt further investigation
would be of value in patients with HIV/AIDS, especially in resource limited environments.