Northampton flanker Calum Clark has been ruled out of England action for a third time in 12 months after he failed to overcome an ankle injury in time to make the tour of Uruguay and Argentina.
England have also lost Leicester lock Ed Slater after he suffered a recurrence of a triceps injury in the Tigers' Premiership final victory over Northampton. Wasps-bound lock Kearnan Myall is the only player to have been called up as a replacement, with England taking 31 players.
In 2012, Clark, 23, was ruled out of England's summer tour of South Africa and the autumn internationals after receiving a record 32-week ban for breaking the arm of Leicester hooker Rob Hawkins.
The England head coach, Stuart Lancaster recalled him for the Six Nations, but a shoulder injury in January sidelined him for the whole tournament. "I feel for him," Lancaster said. "He is desperately unlucky."