A Study to Determine the Immunogenicity and Oral Tolerance to Keyhole Limpet Hemocyanin (KLH)

• T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A) [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
  An SI>=3 after the booster immunization, day 16, will indicate the presence of immune response
  
  
• T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part B) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  An SI <3 after the booster immunization will indicated tolerance.
  
  
• T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A) [ Time Frame: Day 9 ] [ Designated as safety issue: No ]
  
• T cell stimulation index (SI) as measured by 3H-thymidine incorporation after in vitro KLH stimulation of PBMC (Part A) [ Time Frame: Day 16 ] [ Designated as safety issue: No ]
  

• Cytokine secretion profile of T cells stimulated by KLH (Part A) [ Time Frame: Days 0, 9, 16 ] [ Designated as safety issue: No ]
  
• T cell stimulation index measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining after KLH stimulation. (Part A) [ Time Frame: Days 0, 9, 16 ] [ Designated as safety issue: No ]
  
• Suppression (or non-activation) of cytokine secretion profile of T cells stimulated by KLH following oral feeding.(Part B) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  
• Suppression (or non-activation) of T cell stimulation index measured by CFSE staining after KLH stimulation.(Part B) [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  
• Other mechanistic assessments on archived serum samples like anti-KLH antibodies and secreted cytokines.(Part B) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  
• Compare the level of KLH-specific antibodies in the serum (samples from various time points) between Parts A and B. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  

One type of normal immune response is called "oral tolerance." This is when the immune system (the body's natural defense system against illness) turns off (e.g. does not respond) to foods or to other proteins that are eaten. Oral tolerance test is done by feeding people a protein and then vaccinating them with the same protein. Oral tolerance occurs if the vaccination does not cause an immune response.

In this study, oral tolerance of Keyhole Limpet Hemocyanin (KLH) will be tested. KLH is a large protein extracted from a mollusk (a sea animal). The 'native KLH' (which is a large version of this protein) formulation will be used for oral feeding. Immucothel (a smaller version of the KLH protein) will be used for vaccination (injection). Immucothel is an investigational vaccine currently used to treat bladder cancers outside of the US.

Since these particular KLH products have never been used in oral tolerance studies, the investigators want to make sure in this pilot study that they will work as expected in healthy participants before studying these two products in patients with auto-immune disorders.

This study will also determine if Immucothel by itself is strong enough to trigger the immune response. If not, Immucothel will be tested in combination with an adjuvant (a substance that can increase the immune response to a protein like KLH) to determine if an adequate immune response can be seen.

This study consists of two parts. Participants will participate for either 39 days (Part A) or 65 days (Part B). Regardless of the group assignment, a safety follow-up phone call will occur 6 months after the last immunization (189 day for Part A or 215 day for part B) to assess the late onset of adverse events.

Part A of the study will test the experimental vaccine Immucothel by itself or in combination with an adjuvant. Immucothel is a purified protein from a mollusk. Immucothel can be given as a sub-q injection (under the skin) alone or with an adjuvant (a small amount of mineral oil) to help to enhance the immune response. There maybe two groups in this part:

1. Ten participants will be given Immucothel alone by injection on two occasions, If Immucothel alone creates an immune response in most of the participants then Part A will be completed.
2. If Immucothel alone does not create an immune response in most of the participants in Part A, then 10 new participants will be asked to volunteer to test Immucothel in combination with the adjuvant Montanide (mineral oil). This will be given by injection on two occasions If there is an immune response in most of the participants to this combination of Immucothel and Montanide then Part A will be done.

Part B of the study will test the successful Immucothel regimen from Part A with oral KLH. Ten new participants will be given the experimental oral KLH.