**Author details**

*Animal Reproduction in Veterinary Medicine*

induction of ferric citrate transport sytem.

citrate transport system is the major iron acquisition system utilized by *E. coli* [173] to grow in the mammary gland. The mammary gland is an iron-restricted environment, and bovine milk contains approximately 7 mM citrate [185] which is ideal for

Ferric enterobactin receptor, FepA, is an 81 kDa iron regulated outer membrane

protein (IROMP), that binds to ferric enterobactin complex to transoport iron into the bacterial cell [186, 187]. Vaccination of dairy cows with FepA elicited an increased immunological response in serum and milk [188]. Bovine IgG directed against FepA inhibited the growth of coliform bacteria by interfering with the binding of the ferric enterobactin complex [189]. Ferric citrate receptor, FecA, is an 80.5-kDa IROMP that is responsible for the binding of ferric dicitrate [190] and transport into the bacterial cell. The FecA, is conserved among coliforms isolated from cases of naturally occurring mastitis [191]. The iron-regulated outer membrane proteins, FepA and FecA are ideal vaccine candidates because they are surface

Immunization of dairy cows with FepA induced significantly higher serum and whey anti-FepA IgG titers than in *E. coli* J5 vaccinates [188]. Results of *in vitro* growth inhibition studies demonstrated that antibody specific for blocking ferric enterobactin-binding site (anti-FepA) inhibited the growth of *E. coli* in vitro [192]. Cows immunized with FecA did have increased antibody titers in serum and mammary secretions compared with *E. coli* J5 immunization and unimmunized control cows [193, 194]. Antibody purified from colostrum inhibited the growth of *E. coli* when cultured in synthetic media modified to induce FecA expression [193]. Despite their antigenicity, the use of either FepA or FecA alone were not sufficient

Intramammary infection with *E. coli* induced expression and release of proinflammatory cytokines such as TNF-alpha, IL-8, IL-6, and IL-1 [195, 196]. Recently it has been shown with mouse mastitis models that IL-17A and Th17 cells are instrumental in the defense against *E. coli* IMI [197, 198]. However, the role of IL-17 in bovine *E. coli* mastitis is not well defined. Results of a recent vaccine efficacy study against *E. coli* mastitis suggested that cell-mediated immune response has more protective effect than humoral response [199]. The cytokine signaling

The four coliform vaccines which include 1) J-5 Bacterin® (Zoetis, Kalamazoo, MI) [82, 83], 2) Mastiguard®, 3) J Vac® (Merial-Boehringer Ingelheim vet medical, Inc., Duluth, GA) and 4) Endovac-bovi® (IMMVAC) (Endovac Animal Health, Columbia, MO). Of the four coliform vaccines, J-5 Bacterin® and Mastiguard® are believed to have the same component, which is J5 Bacterin. The J Vac® is a different bacterin-toxoid. The Endovac-Bovi® contains mutant *Salmonella typhimurium* bacterin toxoid. All coliform mastitis vaccine formulations use gram-negative core antigens to produce non-specific immunity directed against endotoxin (LPS) [119]. The efficacy of these vaccines has been demonstrated in both experimental challenge trials and field trials in commercial dairy herds [109–111]. The principle of these bacterins is based upon their ability to stimulate the production of antibodies directed against common core antigens that gram-negative bacteria share. These vaccines are considered efficacious even though the rate of intramammary infection is not significantly reduced in vaccinated animals because they significantly reduce the clinical effects of the infection. Experimental challenge studies have demonstrated that J5 vaccines are able to reduce bacterial counts in milk and result in fewer clinical symptoms [109]. Vaccinated cows may become infected with gramnegative mastitis pathogens at the same rate as control animals but have a lower rate of development of clinical mastitis [111], reduced the duration of IMI [110],

to prevent mastitis. The FecA and FepA are antigenically distinct [191].

pathways that lead to efficient bacterial clearance is not clearly defined.

reduced production, culling, and death losses [200, 201].

exposed, antigenic, and conserved among isolates from IMI.

**196**

Oudessa Kerro Dego Department of Animal Science, Institute of Agriculture, The University of Tennessee, Knoxville, TN, USA

\*Address all correspondence to: okerrode@utk.edu

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
