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NATO operative Jacques Kristoff is summoned into action, on his birthday, to track down Galina Konstantin, who has scampered off with an extremely valuable and dangerous top-secret cargo. Finding Galina doesn't take long, and Jacques must wrap up the mission by returning Galina and the contraband to his superiors by train. Jacques's physician wife Madeline isn't happy about this turn of events. But she sees him off at the train station with the couple's teenage daughter Bailey Kristoff and son Ethan Kristoff. Galina's ill-gotten gain is three vials of SP-43, an ultra-virulent strain of smallpox, cultured in fluorescent green serum that contains several other pathogens. A group of terrorists, led by Mason Cole, intend to hijack the train and steal the virus for their own ends. But standing in their way is Jacques. The virus ends up getting loose in the train's ventilation system. Unfortunately, Jacques's family picked this moment to surprise him for his birthday by secretly tagging along for the ride. Jacques becomes a one-man army as he fights to protect his family and the other passengers, and stop Cole and his followers.