Clostridioides difficile Infection (CDI) is a bacterial infection of  the large intestine (colon).  A spectrum of clinical disease ranges from mild diarrhea to severe. CDI is characterized by abdominal pain, fever, diarrhea, nausea, and vomiting. Complications of severe CDI include kidney failure, toxic megacolon, bowel perforation, and death. 

To learn more about C. diff click here.

Clostridioides difficile Life Cycle

The Polyclonal Approach to an area with high unmet medical need.

C. difficile bacteria is a unique pathogen with a complex life cycle that includes spores and vegetative cells producing multiple toxins. The bacteria exist in air, water, soil, processed food and even in human feces. The spores and live vegetative C. diff bacteria causing infection have developed a robust survival mechanism. Studies have demonstrated that the use of antibiotics, which reduces the body’s natural immunity in the gut microbiome, is one of the top factors for primary and reoccurring C. diff infections.  Additional risk factors include previous infection with C. diff, age 65 + years of age, recent stay at a hospital or nursing home and a weakened immune system.

As C. diff continues its attack on the gut, spores transform into vegetative cells which in turn produce toxins and replicate rapidly.  Initial treatments, such as antibiotics, will work on the vegetative cells but not on the spores or toxins.

SAB-195: The first fully-human polyclonal antibody treatment providing superior efficacy for treatment of Clostridioides difficile Infection (CDI)

As demonstrated by SAB pre-clinical studies, [See Figure 1. below] which targeted multiple toxins produced by multiple strains of the C. diff bacteria, including those produced by highly pathogenic strains. SAB’s fully-human polyclonal antibodies  were administered and neutralized the toxins.  Toxins, once neutralized, could no longer harm the digestive tract.  

SAB’s fully-human polyclonal antibodies are highly specific to its target, C. diff bacteria, and don’t attack good microbiome important for a healthy gut. Yet, they bind to more than one epitope, or the part of the C. diff antigen molecule to which an antibody attaches itself, as opposed to monoclonal antibodies (mAbs), which target one receptor. In the case of a monoclonal antibody, if the pathogen mutates, the mAb can no longer attach to a targeted receptor, and therefore lose their efficacy.  

Unlike monoclonal antibodies, polyclonal antibodies sustain their efficacy throughout bacterial evolution or mutation. SAB’s antibodies are fully-human antibodies, they exhibit a long half-life that allows a long-term protection against a disease with a single dose; they also have low risk triggering production of anti-drug antibodies throughout the treatment cycle, the phenomenon well known for non-human antibody treatments and associated with a loss of efficacy and side effects. 

Unlike mAbs, SAB‘s fully-human polyclonal antibodies present a better, broader efficacy solution, because SAB-195 addresses the entire life cycle of the C. diff pathogen.

SAB Clostridioides Difficile Infection Preclinical Data:

CONCLUSION:

Tc bovine-derived anti-quadrivalent toxin hIgG provided 90% to 100% protection in hamsters against CDI strain 630 or more virulent epidemic strain NAP1

Figure 1:  Tc bovine Immunized with Antigen Fusion Proteins Constructed from Receptor Binding Domain of C. diff Toxin A (TcdA), C. diff Toxin B (TcdB)(630) and  (TcdB)(027) and Binary Toxin (CDT)

Reference:

SAB Publication:  “Clostridium difficile chimeric toxin receptor binding domain vaccine induced protection against different strains in active and passive challenge models” Jing-Hui Tian a, Gregory Glenn a, David Flyer a, Bin Zhou a, Ye Liu a, Eddie Sullivan b, Hua Wub, James F. Cummings a, Larry Ellingsworth a,⇑, Gale Smith 

Click here to read full publication:  https://pubmed.ncbi.nlm.nih.gov/28669616/