Immunization routes in cattle impact the levels and neutralizing capacity of antibodies induced against S. aureus immune evasion proteins

Abstract

Vaccines against S. aureus bovine mastitis are scarce and show limited protection only. All currently available vaccines are applied via the parenteral (usually intramuscular) route. It is unknown, however, whether this route is the most suitable to specifically increase intramammary immunity to combat S. aureus at the site of infection. Hence, in the present study, immunization via mucosal (intranasal; IN), intramuscular (triangle of the neck; IM), intramammary (IMM) and subcutaneous (suspensory ligament; SC) routes were analyzed for their effects on the quantity of the antibody responses in serum and milk as well as the neutralizing capacity of the antibodies within serum. The experimental vaccine comprised the recombinant S. aureus immune evasion proteins extracellular fibrinogen-binding protein (Efb) and the leukotoxin subunit LukM in an oil-in-water adjuvant combined with a hydrogel and alginate. The highest titer increases for both Efb and LukM specific IgG1 and IgG2 antibody levels in serum and milk were observed following SC/SC immunizations. Furthermore, the harmful effects of Efb and leukotoxin LukMF’ on host-defense were neutralized by serum antibodies in a route-dependent manner. SC/SC immunization resulted in a significant increase in the neutralizing capacity of serum antibodies towards Efb and LukMF’, shown by increased phagocytosis of S. aureus and increased viability of bovine leukocytes. Therefore, a SC immunization route should be considered when aiming to optimize humoral immunity against S. aureus mastitis in cattle.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0243-7) contains supplementary material, which is available to authorized users.

LukMF′ is the major secreted leukocidin of bovine Staphylococcus aureus and is produced in vivo during bovine mastitis

“…Naturally occurring bovine antibodies specific for LukM have been shown to neutralize LukMF′ killing in vitro 26, therefore, antibody levels against LukM at challenge were included in the models. Since IgG1 is much more abundant in milk than IgG227, the effects of IgG1 and IgG2 LukM specific antibody levels were tested separately.…”

“…LukM levels were probably below the detection limit before day 7, considering that dairy cows produce around 30 liters of milk per day, which leads to strong dilution of the toxin. Bovine serum antibodies have been shown to neutralize LukMF′ killing in vitro 26. However, antibody levels in milk are low as compared to serum and the concentration of LukMF′ at foci of infection may be higher than the limited neutralizing capacity of milk antibodies, which could explain why there was no effect of LukM antibody levels at challenge on the course of infection.…”

From Separated Laws and Directives to a Unique Regulatory Issue in Europe about the Synergic and Conflicting Use of Subsurface to Produce Low Carbon Energy

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Implications of Intranasal Polyvalent Vaccination for Pulmonary Alveolar Macrophage and Neutrophil Functions in Calves

“…Mucosal immunization was implemented because it was shown to be effective in calves and had less interference from maternal antibodies [18,47,48]. The commercial vaccine (CattleMaster Gold FP 5/L5, P zer Animal Health, Montreal, Canada) used contains a lyophilized preparation of modi ed live strains of IBR, PI3, and BRSV, inactivated BVDV types 1 and 2 and inactivated cultures of ve Leptospira sp.…”