Schematic of VLP vaccination of preimmune ferrets. (A) Ferrets (n = 4) were infected with one of various H1N1 viruses (106 PFU). At day 84 and again at day 168, ferrets were vaccinated with VLP vaccines expressing either COBRA or wild-type HA antigens. Serum samples were collected at day 14, 86, 98, 168, and 182 postinfection. (B) A separate set of Sing/86 preimmune ferrets were vaccinated with a single VLP vaccine at day 84. At day 168, the ferrets were challenged with A/California/07/2009 (106 PFU) and monitored for morbidity and mortality for 14 days postinfection. Blood was collected prior to initial infection and at days 14, 84, 98, 168, and 182 postinfection. Nasal washes were collected at days 0, 1, 3, 5, and 7 to assess viral titers.