The loose head prop has been ruled out of the remainder of the 2019 tournament with an ankle ligament injury.
Vunipola picked up the injury during England’s win against France on Sunday and is expected to be out for 10 weeks.
England head coach Eddie Jones said: “It is obviously very disappointing to lose Mako at this stage as he is an important player for us but it does provide an opportunity for the team to grow.”
Vunipola has made a huge impact for England so far in the tournament. He missed just one of his 39 tackles and has made 23 carries in the 119 minutes of play against Ireland and France.