Immunisation of mares with binding domains of toxinsAandBofClostridium difficileelicits serum and colostral antibodies that block toxin binding

Abstract

Results of studies support the feasibility of a prepartum vaccine against C. difficile enterocolitis in foals.

Equine hyperimmune serum protects mice againstClostridium difficilespore challenge

“…Polyclonal antibodies are especially effective for neutralizing and clearing toxins from the bloodstream; this is remarkable as there is a significant level of sequence diversity among members of large toxin families [31]. Recently, Artiushin et al [3] found that immunization of pregnant mares with receptor-binding domains of toxins A and B can lead to the generation of specific antibodies in serum and colostrum that can block the cytopathic activity of the toxins in vitro . With the goal of providing an effective strategy for developing a prophylaxis for CDI in horses, we produced antibodies of equine origin with toxin-neutralizing activity and demonstrated their efficacy in vivo to prevent CDI induced by C. difficile of equine origin.…”

“…The ability of these antibodies specific for C. difficile toxins to prevent clinical disease and reducing carriage of C. difficile was tested in hamster and gnotobiotic mouse models. However, there are no reports of the use of vaccines or immunotherapeutic agents against equine CDI [3]. To develop anti- C. difficile antiserum for the treatment of horses with C. difficile -associated disease, we prepared antisera of equine origin against both C. difficile toxins A and B as well as the whole bacteria.…”

Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections

“…Immunization of pregnant mares and cows with C. difficile proteins results in the production of antibodies that can be obtained from the colostrum and used therapeutically. Colostrum from mares immunized with toxins A and B binding domains was able to block the cytotoxic activity of the C. difficile toxins A and B . Repeated immunization of a pregnant cow with recombinant mutants of toxin A and B produced hyperimmune bovine colostrum (HBC) that was able to reduce the disease severity of CDI in piglets .…”

“…Colostrum from mares immunized with toxins A and B binding domains was able to block the cytotoxic activity of the C. difficile toxins A and B . Repeated immunization of a pregnant cow with recombinant mutants of toxin A and B produced hyperimmune bovine colostrum (HBC) that was able to reduce the disease severity of CDI in piglets . Similarly, HBC was shown to prevent, treat, and reduce recurrence of CDI in mouse models .…”

“…117 Repeated immunization of a pregnant cow with recombinant mutants of toxin A and B produced hyperimmune bovine colostrum (HBC) that was able to reduce the disease severity of CDI in piglets. 117 Similarly, HBC was shown to prevent, treat, and reduce recurrence of CDI in mouse models. 118 A phase II/III clinical trial (NCT00747071) to test the efficacy and safety of colostrum-derived antibodies for the prevention of CDI was withdrawn.…”