Lloyd Mayer | Mount Sinai Hospital | New York, NY

Mt. Sinai School of Medicine | New York, NY

The hallmark of immune response in the intestine is one of tolerance or active suppression of immunity against non-pathogens (commensal flora, dietary antigens). This phenomenon was described in 1911 when Wells fed hen egg proteins to guinea pigs and found them to be resistant to anaphylaxis when challenged. Subsequently, numerous studies have found that animals that were fed proteins such as ovalbumin or sheep erythrocytes do not respond as well to these antigens when subsequently immunized but do respond normally to other antigens. Induction of tolerance to orally administered antigens has also been demonstrated in humans using the neoantigen Keyhole Lymphocyte Antigen (KLH).

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease characterized by an assumed loss of the normally tolerant state of the mucosal immune system. Previous work by the investigators of this study has demonstrated defects in the development of oral tolerance to KLH in IBD patients. They also revealed that the defect in oral tolerance is not limited to IBD patients, but is also seen in unaffected first-degree relatives of Crohn’s disease patients, suggesting that defects in tolerance are genetically regulated and may predispose to the development of IBD. If true, this raises the possibility of defects in oral tolerance induction in patients with other autoimmune diseases.

As a first step in characterizing the mechanisms of oral tolerance and its potential role in autoimmunity, this pilot study will determine the ability of Biosyn’s KLH to induce oral tolerance in healthy volunteers. Specifically, it aims to 1) determine whether Biosyn native KLH (Immucothel) can induce tolerance when administered orally, and 2) determine the immunogenicity of Immucothel and whether an adjuvant (Montanide) is necessary for an immune response. KLH will be tested in healthy participants in whom the oral tolerance response is known to be intact.

This is a two-part, single site, open label, pilot study. The goal of Part A is to determine the immunogenicity of Immucothel. Results from Part A will establish whether Immucothel will be used alone or with Montanide (adjuvant) in Part B in new participants. The goal of Part B is to test whether the native oral KLH preparation from Biosyn can induce tolerance in healthy participants when administered prior to immunization.

To further uncover the relationship between oral tolerance and autoimmunity the investigators plan on conducting an oral tolerance induction study in patients with IBD, type 1 diabetes, multiple sclerosis, and ankylosing spondylitis as a separate study.