SAN DIEGO, CA—Vaccines in tablet form delivered to a mucosal site provide both practical and immunologic advantages, Wendy Peters, PhD, from Vaxart Inc., South San Francisco, CA, explained at IDWeek 2015.
Many prophylactic vaccines are given parenterally and require cold chain storage and medical personnel for administration. Dr. Peters and her colleagues reported on the development of a novel influenza tablet vaccine platform stable at room temperature. The vaccine was created using a non-replicating Adenovirus type 5 (Ad5) backbone and a toll-like receptor-3 (TLR3) agonist as an adjuvant.
The study authors completed two randomized, placebo-controlled clinical trials to evaluate the immunogenicity and safety of a prophylactic influenza vaccine (n=61). Patients were given enteric-coated tablets containing either placebo, 1e9, 1e10, or 1e11 infectious units (IU) of vaccine vector.
An additional study in 24 subjects was conducted to determine the optimal immune induction region in the small intestine using 1e11 IU liquid vaccine and the InteliSite Companion Capsule, a radiofrequency-activated delivery device.
In all three studies, peripheral mononuclear blood cells (PBMCs) were isolated at baseline and Days 7, 14, and 28 following vaccination. Samples were tested for systemic T-cell responses to influenza hemagglutinin (HA) by interferon-gamma and granzyme B (GrB) Elispot assays. In addition, study authors performed multicolor flow cytometry to measure polyfunctional T-cells.
Results showed that the tablet vaccine was safe, demonstrating an adverse event profile similar to placebo. All of the adverse events were mild except for one moderate headache and abdominal pain, they reported, and there were no vaccine-related severe adverse events.
A significant increase in numbers of spot forming interferon-gamma cells were seen at every dose level and time point tested in comparison to baseline responses. Peak GrB responses were significantly greater than baseline at the 1e9 IU and 1e10 IU dose levels.
Anti-Ad5 titers did not increase after vaccination, Dr. Peters noted. Higher peak mean responses were seen in the ileum vs. the jejunum when liquid vaccine was directly delivered. Both induction sites, however, demonstrated significantly increased T-cell responses over baseline.
Data across the three studies suggest that the 1e11IU dose delivered to the ileum will induce the most robust immune response.
“These first-in-man clinical trials testing an influenza tablet vaccine have displayed a favorable safety and tolerability profile and a dose-dependent and multifunctional T cell response,” she concluded.