This is a Phase 1/2, randomized, observer-blinded, active-controlled trial. Approximately 330 eligible subjects will be enrolled and randomized into 1 of 3 treatment groups as shown in the Trial Design table below. Each group will consist of approximately 110 subjects total, stratified by age, gender, and history of receipt of 2016 - 17 influenza vaccine. On Day 0, subjects in Groups A and B will be administered an IM injection of NanoFlu at one of two dose levels; subjects in Group C will receive the preconfigured comparator (Fluzone HD) at the manufacturer's recommended dose and volume.

On Day 21, all Group A and B subjects will be administered a rescue injection with a licensed seasonal influenza vaccine, while all Group C subjects will be administered an injection with sterile saline placebo to maintain trial blind. Trial follow-up for each subject will span approximately 1 year from the Day 0.