Cholera Toxin B Subunit (CTB) Administered by Mucosal Way in Healthy Adult Volunteer
Condition: Infection
MeSH terms: Cholera
Study type: Interventional
Phase: Phase 1

Summary: 
      It is a biomedical research without direct individual benefit, exploring and comparing the
      mucosal immune response after oral, nasal and sublingual administration of B-subunit of
      non-toxic cholera toxin (CTB) in healthy adult volunteers.
    

Detailed description: 
      The immense majority of the infections involve the mucosal surfaces as a gateway of the
      pathogenic agent. These mucosal surfaces are mainly represented by the gastrointestinal,
      respiratory and urogenital tract. These mucosal surfaces contain a highly developed immune
      system, which can exploit in a mucus vaccine approach to fight against infectious agents upon
      their penetration in the body. It has been established that to be effective against infection
      mucosa, a vaccine must stimulate the local immune system. This objective is reached much more
      efficiently when the vaccine is administered by mucosal way (oral, nasal) than by the
      parenteral classical way. Recent works allowed developing a new non invasive system of
      administration of vaccines. It is based on the mucosal administration (oral, nasal, rectal,
      vaginal) comprising a combination of antigen bound (either chemically or by genetic fusion)
      to the non-toxic subunit of cholera toxin or CTB (Cholera Toxin B subunit). This subunit has
      an exceptional affinity for GM1 ganglioside expressed on the surface of all nucleated cells.
      So, the mucosal administration (by oral or nasal route) of a low dose of an antigen linked to
      the CTB - Mucosal vector with immunomodulatory properties - Leads powerful secretor immune
      responses in the exposed mucous As well as in distant mucous, with a strong production of
      secretories IgA.

      The developed methods of exploration have to allow to characterize the cells which live (or
      which migrate) in the mucous membrane investigated on the functional and phenotypic plan.

      This research should lead to a range of standardized operating procedures, allowing to
      evaluate the immunogenicity of vaccines candidates to the mucous administration and of
      predictive markers of the type of immune response generated.

      The main objective of the study is to analyse at the healthy voluntary subjects the
      systematic immunizing answer induced after nasal, oral or sublingual administration of the
      CTB from blood samples - the lymphoid "compartment" the most accessible at the man- from
      saliva and from nasal wash. The immune response after administration of the CTB By sublingual
      way should be comparable in that of two other ways in term of intensity of the response,
      however, with a different IgA / IgG report.

      The secondary objective of the study is to establish a range of tests to predict the
      character and the intensity of this response by analyzing the expression of B cells certain
      surface molecules marking their future for the production of Antibodies.

      It is a regional prospective monocentric study conducted in opened without direct individual
      profit. The study will be conducted over 3 years including 24 months of recruitment for each
      patient with a follow-up of 35 days and 6 months of operation data.
    

Intervention name(s): CTB by nasal way; absorption of CTB by oral way; absorption of dukoral by oral way; absorption of CTB by sublingual way; absorption of CTB by sublingual way
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): absorption of CTB by oral way; absorption of dukoral by oral way; absorption of CTB by sublingual way; absorption of CTB by sublingual way
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: immune response; b-subunit of cholera toxin; mucosal way; healthy volonteers; vaccine