A Phase 2 Influenza A Challenge Study Following Oral Administration of an H1N1 HA Ad-Vector Seasonal Flu Vaccine

This is a Phase 2 randomized, placebo- and active-controlled, two-part study in which healthy adult volunteers with low or undetectable pre-existing antibodies against A/California/7/2009(H1N1) pdm09-like virus will be challenged with an influenza A/H1N1 human challenge strain approximately 90 days after vaccination with a single dose of H1N1 HA Adenoviral-vector based seasonal influenza vaccine and dsRNA adjuvant (VXA-A1.1), an injectable QIV vaccine, and/or placebo. An independent Safety Monitoring Committee (SMC) will oversee the safety of the study. To accommodate the limited size of the isolation unit that will be utilized for the challenge and post-challenge sequestration period, subjects will move through the study (enrollment, vaccination and challenge) sequentially in a total of 6 cohorts. Each cohort will randomize 30 subjects to obtain approximately 25 subjects per cohort for the challenge phase. Subjects will be randomized in a ratio of 2:2:1 (VXA-A1.1: Quadrivalent Influenza Vaccine (QIV): Placebo. The study will be conducted in two parts. Part A: Subjects will be randomized in a double-blinded manner to receive a single administration of one of three treatment arms: * Arm 1: VXA-A1.1 oral vaccine + placebo Intramuscular (IM) * Arm 2: QIV (IM) injection + oral placebo * Arm 3: Placebo IM injection + oral placebo Subjects will return to the site for \~8 visits and be contacted remotely at defined time points to be followed for immunogenicity and safety during study Part A. Part B: Subjects will be challenged with a wild-type influenza A H1 virus strain \~90 days following vaccination. Blood samples will be collected to evaluate immunogenicity. Subjects will remain in the isolation unit for 6 to 9 days post-challenge. Following challenge, influenza symptoms and signs will be assessed during the sequestration period. Blood samples and nasopharyngeal swab samples will be collected. Vital signs will be measured every 4 hours during waking hours. After release from the isolation unit subjects will return to the site 30 days post-challenge. Part B will continue for purposes of collecting long term safety follow-up (serious adverse events (SAEs), AEs of special interest (AESIs) and any new onset of chronic illness (NOCI) via phone contacts through 1 year post-vaccination (Day 365).