Four- to six-month-old male ferrets were injected i.m. with PBS, Fluarix (2016–2017 formulation), or HA from A/California/07/09 adjuvanted with soluble cGAMP (15 μg) or monoaxial Ace-DEX cGAMP MPs (15 μg cGAMP in 1.5 mg MPs). Animals received a boost with the same formulation 4 weeks later. (A) Serum was collected post boost (Day 49) and virus neutralizing titers against A/California/07/2009 were assessed. Ferrets were challenged intranasally with 1.25 × 107 FFU of Cali/07/09. Nasal lavage was collected (B) day 2 and (C) day 4 post challenge and viral load was assessed by foci forming assay. (D) Animal weights and (E) the periodic combined clinical index, a composite measure of animal activity and respiratory index (sneezing and nasal discharge), were assessed daily for 18 days following infection following infection. (n=4 ± SD, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).