Friday, July 17, 2015: 10:45 AM
Hall Berlin C, Ground Floor (Maritim Hotel)
Background: The development of a tablet vaccine has been hampered by the lack of robust models of human gastrointestinal biology. Stomach acid can destroy pH sensitive vaccines, and enteric coatings that protect vaccines against acid degradation work in a species-specific fashion. For a vaccine embedded in tablets, if no immune response to antigen was observed post administration, it would be unclear on whether the biology or the enteric coating failed. Method: In order to explore vaccine performance independent of enteric coating, a small molecule drug development technique using radio-controlled capsules (RCC) delivered to the intestine was explored in a clinical trial. Mechanical capsules were filled with a recombinant adenoviral vector expressing influenza HA and a radio labeled tracer. These capsules were swallowed by human volunteers, tracked by scintigraphy, and opened remotely in either the ileum or the jejunum for the purpose of determining the best performing location. Results: Substantial numbers of mucosal homing, antigen specific B cells were found 7 days after immunization in the peripheral blood of all immunized volunteers, with up to 15% of B cells having alpha4beta7 high expression compared with 2% at day 0. One location had superior performance, and the HAI seroconversion rate was 67% in this group. Further, fecal samples and nasal washes of subjects immunized by RCC demonstrated increases in the specific antibody responses to influenza. Conclusion: These results demonstrate that the biology of the vaccine can elicit typical influenza vaccine immune responses in serum as well as very potent mucosal antibody responses.