This study has demonstrated that the tablets containing BCP with high titers of antibodies against ETEC can provide protection against the development of diarrhea following the ingestion of a homologous ETEC strain. Importantly, the efficacy of the treatment was not significantly reduced by the omission of sodium bicarbonate buffer, which would be expected to protect the BCP preparation from stomach acid. The finding that bicarbonate buffer was not needed for this preparation may be explained by the fact that the proteins in cow's milk can provide sufficient buffering on their own [18
]. Further examination of this finding has led to the discovery that non-antibody proteins in colostrum can protect the antibodies themselves and potentially other delicate moieties in acid environments such as the stomach. This finding is further described in Australian Patent 2003212098 and US Patent 2005/0175597 (http://www.freepatentsonline.com/y2005/0175597.html
The studies reported here emulated the ability of a tablet formulation of BCP to prevent diarrhea in someone eating a contaminated meal. The results showed that when taken before eating or drinking contaminated food or drink, the tablet formulation can protect travelers from symptomatic infection with ETEC of a homologous serotype. The results are consistent with the hypothesis that the tablet formulation allowed delivery of protective antibodies to the small intestine, which is the site of infection with ETEC [3
]. As the vaccine used to immunize cattle did not contain ETEC enterotoxins and the BCP preparation did not contain antibodies to these toxins (data not shown), the anti-ETEC activity of the BCP was most likely due to its ability to interfere with the binding of ETEC cells to the intestinal mucosa [3
]. This hypothesis is supported by the fact that the BCP preparation did not interfere with the viability of the challenge strain.
As in other studies, which have investigated the use of orally administered hyperimmune bovine colostrum or milk immunoglobulin for a variety of conditions [19
], no adverse effects were ascribed to the BCP preparation that was used in this study. Published reports of the use of hyperimmune bovine colostrum or milk immunoglobulin to prevent or manage GIT infections caused by rotavirus, Cryptosporidium, Clostridium difficile, Shigella flexneri, Helicobacter pylori
and ETEC have provided conflicting results [9
]. Some studies failed to demonstrate a protective effect of these preparations [10
], whereas others showed that they can provide protection against the development of clinical manifestations of infection or significantly decrease their severity [9
]. The doses of hyperimmune colostrum concentrates in some of these studies were as high as 10 g per day, in contrast to our study which used 0.6–1.2 g of a similar extract per day.
Studies using colostral proteins to reduce gastrointestinal damage after non-steroidal anti-inflammatory drug therapy have pointed toward the presence of intrinsic growth factors in bovine colostrum (such as epidermal growth factor), and broad-spectrum antimicrobial factors (such as lactoferrin) that may have a beneficial effect on the health of the intestinal mucosa [29
]. Possibly, the success of tablets made from BCP in protecting against challenge with ETEC was partly due to the effect of increased mucosal resistance caused by some of these bioactive factors in addition to the specific anti-ETEC antibodies. It is most unlikely, however, that the action of these other bioactive factors alone can explain our findings, since several studies have demonstrated that while non-immune colostrum or milk extract may assist recovery from gut damage, it has little effect on the prevention of infectious diarrhea [9
In conclusion, this study has demonstrated that a novel tablet formulation of hyperimmune BCP containing antibodies against 14 different ETEC strains can significantly reduce the risk of diarrhea following exposure to a homologous ETEC strain. The beneficial effect of BCP was independent of the concurrent use of a sodium bicarbonate buffer to aid passage of the active product through the stomach. These results indicate that practicable formulations of hyperimmune colostrum can reduce the risk of ETEC-induced diarrhea in travelers to high-risk destinations.