Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products

Sears, Khandra T.; Tennant, Sharon M.; Reymann, Mardi; Simon, Raphael; Konstantopoulos, Nicky; Blackwelder, William C.; Barry, Eileen M.; Pasetti, Marcela F.

doi:10.1128/cvi.00186-16

Cited by 23 publications

(21 citation statements)

References 46 publications

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“…However, further experiments would be required to understand the exact mechanism why IMM-124E is most effective at 100mg/kg. A recent study that investigated how IMM-124E might exert its anti-diarrheagenic effects, demonstrated that IMM-124E has direct anti-bacterial activity via inhibition of growth and migration of bacteria 21 . This indicates that also during colitis, the beneficial effect of IMM-124E is possibly due to direct anti-bacterial properties, which might lead to decreased translocation of invading pathogens.…”

Section: Discussionmentioning

confidence: 99%

“…IMM-124E is a bovine colostrum-based product obtained from cows that have been immunized with LPS from Escherichia coli, which results in high levels of LPS-specific IgG. A study investigating the composition of IMM-124E has been published recently, showing that 1mg IMM-124E powder contains about 0.4mg total IgG, which is comparable to the total IgG content in colostrum powder 21 . In previous studies, it has been demonstrated that administration of IMM-124E ameliorates disease in a model of non-alcoholic steatohepatitis (NASH) 22,23 , a disease where chronic presence of LPS and subsequent low-grade inflammation might promote disease activity 24,25 .…”

Section: Introductionmentioning

confidence: 99%

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Administration of the Hyper-immune Bovine Colostrum Extract IMM-124E Ameliorates Experimental Murine Colitis

Spalinger

Atrott

Baebler

et al. 2018

Journal of Crohn's and Colitis

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Background/Aims Inflammatory bowel disease (IBD) is accompanied by lesions in the epithelial barrier, which allow translocation of bacterial products from the gut lumen to the host's circulation. IMM-124E is a colostrum-based product, containing high levels of anti-E.coli-LPS IgG and might limit exposure to bacterial endotoxins. Here, we investigated whether IMM-124E can ameliorate intestinal inflammation. Methods Acute colitis was induced in WT C57Bl/6J mice by administration of 2.5% DSS for 7 days. T cell transfer colitis was induced via transfer of 0.5x10 6 naïve T cells into RAG2-/-C57Bl/6J mice. IMM-124E was administered daily by oral gavage either preventive or therapeutically. Results Treatment with IMM-124E significantly ameliorated colitis in acute DSS colitis and in T cell transfer colitis. Maximum anti-inflammatory effects were detected at an IMM-124E concentration of 100 mg/kg body weight, while 25 mg/kg and 500 mg/kg were less effective. Histology revealed reduced levels of infiltrating immune cells, and less pronounced mucosal damage. Flow cytometry revealed reduced numbers of effector T helper cells in the intestine, while levels of regulatory T cells were enhanced. IMM-124E-treatment reduced the DSS-induced increase of serum levels of LPS-binding protein, indicating reduced systemic LPS exposure. Conclusions Our results demonstrate that oral treatment with IMM-124E significantly reduces intestinal inflammation, via decreasing the accumulation of pathogenic T cells, and concomitantly increasing the induction of regulatory T cells. Our study confirms the therapeutic efficacy of IMM-124E in acute colitis and suggests that administration of IMM-124E might represent a novel therapeutic strategy to induce or maintain remission in chronic colitis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Administration of the Hyper-immune Bovine Colostrum Extract IMM-124E Ameliorates Experimental Murine Colitis

Spalinger

Atrott

Baebler

et al. 2018

Journal of Crohn's and Colitis

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“…Recently, preventive methods to reduce the risk of ETEC-induced diarrhea have been proposed. A hyperimmune bovine colostrum (HBC) produced by immunization of cows during gestation has proven clinically effective in preventing ETEC diarrhea (Sears et al, 2017 ). Among non-antibiotic therapies, vaccine development is a strategy of choice but, to date, there is no universal or specific licensed vaccine against InPEC.…”

Section: Introductionmentioning

confidence: 99%

Intestinal Pathogenic Escherichia coli: Insights for Vaccine Development

Rojas-López

Monterio

Pizza³

et al. 2018

Front. Microbiol.

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Diarrheal diseases are one of the major causes of mortality among children under five years old and intestinal pathogenic Escherichia coli (InPEC) plays a role as one of the large causative groups of these infections worldwide. InPECs contribute significantly to the burden of intestinal diseases, which are a critical issue in low- and middle-income countries (Asia, Africa and Latin America). Intestinal pathotypes such as enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) are mainly endemic in developing countries, while ETEC strains are the major cause of diarrhea in travelers to these countries. On the other hand, enterohemorrhagic E. coli (EHEC) are the cause of large outbreaks around the world, mainly affecting developed countries and responsible for not only diarrheal disease but also severe clinical complications like hemorrhagic colitis and hemolytic uremic syndrome (HUS). Overall, the emergence of antibiotic resistant strains, the annual cost increase in the health care system, the high incidence of traveler diarrhea and the increased number of HUS episodes have raised the need for effective preventive treatments. Although the use of antibiotics is still important in treating such infections, non-antibiotic strategies are either a crucial option to limit the increase in antibiotic resistant strains or absolutely necessary for diseases such as those caused by EHEC infections, for which antibiotic therapies are not recommended. Among non-antibiotic therapies, vaccine development is a strategy of choice but, to date, there is no effective licensed vaccine against InPEC infections. For several years, there has been a sustained effort to identify efficacious vaccine candidates able to reduce the burden of diarrheal disease. The aim of this review is to summarize recent milestones and insights in vaccine development against InPECs.

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“…It may be that colostrum-derived antibodies, due to their intrinsic nature, are able to survive the orogastric delivery route better, thereby providing more active antibody to the gut. 35 While not addressed in this study, it would be of value to determine the amount of functional antibody available in the gut following ingestion. Consistent with the data seen here, we previously observed a low number of anti-CS6 responders after oral challenge with CS6+ ETEC B7A strain (K. Talaat et al, submitted for publication).…”

Section: Discussionmentioning

confidence: 99%

Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenicEscherichia colias a prophylactic against diarrhea

et al. 2020

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Background. Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A. Methods. This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 10 10 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD). Results. A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups. Conclusions. Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrumderived antibodies.

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Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products

Cited by 23 publications

References 46 publications

Administration of the Hyper-immune Bovine Colostrum Extract IMM-124E Ameliorates Experimental Murine Colitis

Administration of the Hyper-immune Bovine Colostrum Extract IMM-124E Ameliorates Experimental Murine Colitis

Intestinal Pathogenic Escherichia coli: Insights for Vaccine Development

Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenicEscherichia colias a prophylactic against diarrhea

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