Methods: We have completed 2 randomized phase I placebo controlled clinical trials to test the safety and immunogenicity of a prophylactic Influenza vaccine. A total of 56 subjects were enrolled and dosed with enteric-coated tablets containing either placebo, 1e9, 1e10 or 1e11infectious units (IU) of vaccine vector. In addition, a study was performed to determine the optimal immune induction region of the small intestine (SI) using liquid vaccine and a radio frequency activated drug delivery device (InteliSite Companion Capsule). For all 3 studies PBMCs were isolated at baseline and days 7, 14 and 28 post vaccination, and were tested for systemic T cell responses to influenza hemagglutinin (HA) by IFN-γ and granzyme B (GrB) Elispot assays. Multicolor flow cytometry was also performed to measure polyfunctional T cells.
Results: The tablet vaccine was found to be safe with an adverse event profile indistinguishable from placebo. At each dose level, and at each time point tested, there were significant increases in numbers of spot forming IFN-γ cells as compared to baseline responses. Peak GrB responses were also significantly increased over baseline at the 1e9 and 1e10 IU dose levels. Importantly, from a platform perspective anti-Ad5 titers did not increase after vaccination. In addition, direct delivery of liquid vaccine to two sites in the SI resulted in higher peak mean responses in the ileum compared to the jejunum, but both induction sites had significantly increased T cell responses over baseline levels. Taken together the results from all 3 trials suggest that a dose of 1e11IU delivered to the ileum will elicit the most robust immune response.
Conclusion: There are both practical and immunologic advantages to delivering vaccines in tablet form to a mucosal site. These first in man clinical trials have displayed an excellent safety profile and substantial systemic T cell immunity.
J. Martinez, Vaxart Inc: Employee , Salary
L. Kim, Vaxart inc: Employee , Salary
S. Tucker, Vaxart Inc: Board Member and Employee , Salary