Joe Cokanasiga will provide firepower to England's back line in the absence of Manu Tuilagi after being picked on the left wing for Thursday's World Cup clash with the USA.
Cokanasiga replaces Jonny May in one of 10 changes to the starting XV that launched the Pool C campaign with an underwhelming 35-3 victory over Tonga in Sapporo.
The rampaging Fijian-born 21-year-old has been struggling with a knee injury but has been passed fit for the second match of England's four-day turnaround.
Cokanasiga's presence makes up for Tuilagi being omitted from the 23 after the Leicester wrecking ball laid waste to Tonga with a devastating two-try salvo and series of marauding runs.
Vunipola started throughout the warm-up series and continues his run of games after a frustrating spell of injury that saw him suffer three broken arms in a year.
Henry Slade is absent despite making his comeback against Tonga after three months out with a knee injury incurred during last season's Gallagher Premiership final.
Slade came on at full-back at the Sapporo Dome and hurt the same knee that resulted in his summer on the sidelines but was able to finish the match after receiving treatment.
Coach Eddie Jones said: "The four-day turnaround is something we experimented with against Japan last autumn and so the players have had some experience of it.
"You have to make sure the two days before the game are exactly the same as you would normally have for any other game.
"What I see now is players handling it really well but the game on Thursday will be the litmus test.
"It is our best 23 and we have looked at some players that would benefit not playing in this game, so have kept them out of the 23.
"But it is a great opportunity for another set of players to do the team proud."
"USA are a tough, physical team who are extremely well coached by Gary Gold. There are a number of players who our guys know really well and are a team we respect."