Cholera Toxin B: One Subunit with Many Pharmaceutical Applications

Abstract

Cholera, a waterborne acute diarrheal disease caused by Vibrio cholerae, remains prevalent in underdeveloped countries and is a serious health threat to those living in unsanitary conditions. The major virulence factor is cholera toxin (CT), which consists of two subunits: the A subunit (CTA) and the B subunit (CTB). CTB is a 55 kD homopentameric, non-toxic protein binding to the GM1 ganglioside on mammalian cells with high affinity. Currently, recombinantly produced CTB is used as a component of an internationally licensed oral cholera vaccine, as the protein induces potent humoral immunity that can neutralize CT in the gut. Additionally, recent studies have revealed that CTB administration leads to the induction of anti-inflammatory mechanisms in vivo. This review will cover the potential of CTB as an immunomodulatory and anti-inflammatory agent. We will also summarize various recombinant expression systems available for recombinant CTB bioproduction.

Interaction of Cholera Toxin B Subunit with Intestinal Epithelial Cells

“…Recombinant CT-B has been recently found to suppress immunopathological reactions in allergy and autoimmune diseases to stimulate humoral immunity and to induce anti inflammatory responses in vivo, in particular, to mitigate the intestinal inflammation of Crohn's disease in mice and humans [25,29,2,28]. Since CT-B can prevent infection but also autoimmune reactions, the question is how these two apparently opposite immune reactions can be achieved by the same protein.…”

Vaccination via Chloroplast Genetics: Affordable Protein Drugs for the Prevention and Treatment of Inherited or Infectious Human Diseases

“…Functional CTB is a homopentamer that enters target cells by binding the GM1 ganglioside, which is present in membranes of intestinal epithelial cells, neurons, and immune cells, among others (5, 37, 76, 81). Binding to GM1 causes retrograde trafficking of CTB through the cell and into the ER (5, 73). Alternatively, the entire CTB-GM1 complex may be transcytosed across the intestinal epithelium (113).…”

Cold chain and virus‐free oral polio booster vaccine made in lettuce chloroplasts confers protection against all three poliovirus serotypes

“…Fusion of antigens with GM1 ganglioside receptor-binding protein CTB (cholera non-toxic subunit B) facilitates efficient delivery of vaccine antigens to the immune system (Chen et al, 2015;Gupta et al, 2015;Kumar and Daniell, 2004;Xiao et al, 2016). GM1 is broadly distributed in a variety of cell types including epithelial cells of the gut and antigen-presenting cells, macrophages, dendritic cells, and B cells allowing the fusion antigens to efficiently cross the mucosal barrier via the GM1-ganglioside receptor and provides optimal access to the immune system (Baldauf et al, 2015;Stratmann, 2015). This delivery system was first developed in tobacco chloroplasts but in the past several years lettuce system has been advanced to express several vaccine antigens including cholera, malaria (Davoodi-Semiromi et al, 2010), dengue (Kanagaraj et al, 2011), plague (Arlen et al, 2007), tuberculosis (Lakshmi et al, 2013) and anthrax (Koya et al, 2005;Ruhlman et al, 2010).…”