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Twickenham - England coach Eddie Jones named a squad featuring eight uncapped players on Thursday for the reigning champions Six Nations opener away to Italy in next month.
Injuries and suspensions have robbed Jones of several senior players for the match in Rome on February 4.
No 8 Billy Vunipola is set to miss the entire tournament with a shoulder injury, while fellow back-row James Haskell and prop Joe Marler have both been ruled out of the Italy fixture and the following week's clash against Wales because of suspensions received while on club duty.
Following this weekend's club fixtures, 35 players will travel to Portugal for a week-long training camp before reconvening on Monday 29 January at England's Pennyhill Park training base ahead of the Championship opener.
Although there are several newcomers, the rest of Jones's squad have 898 Test caps between them, with England bidding to make history by becoming the first side to win a third successive outright Championship title.
Harlequins prop Lewis Boyce is called up for the first-time following club colleague Marler's six-week ban.
Meanwhile Gary Graham is retained having been involved in the England setup for the first time earlier this month and Alec Hepburn of Exeter receives his first call-up to the senior squad.
Backs Nathan Earle (Saracens) and Harry Mallinder (Northampton) have also named after they both travelled on England's tour of Argentina in June without playing.
This was Jones's first England squad since the Rugby Football Union announced on Wednesday that the Australian's contract was being extended until 2021.
"I have selected the strongest available squad to prepare for our opening match against Italy," said Jones.
Dylan Hartley, the England captain, remained in the squad despite the hooker's performances for Northampton this season coming in for criticism.
England are yet to lose a Test to the Italians and Jones said: "It is important we start the tournament well and we will spend the next two weeks training smart and really fine-tuning our game plan for the Italy match next month.
"I am expecting a really positive training camp in Portugal and while we have a few players unavailable through injury or suspension, it has provided opportunity for others who will be desperate to be involved in the Italy game."
England squad:
Backs:
Fullbacks/wings: Mike Brown (Harlequins), Nathan Earle (Saracens), Harry Mallinder (Northampton), Jonny May (Leicester), Denny Solomona (Sale), Anthony Watson
Inside backs: Danny Care (Harlequins), Owen Farrell (Saracens), George Ford (Leicester), Jonathan Joseph (Bath), Alex Lozowski (Saracens), Jack Nowell (Exeter), Henry Slade (Exeter), Ben Te'o (Worcester), Marcus Smith (Harlequins), Ben Youngs (Leicester)
Forwards:
Back five: Gary Graham (Newcastle), Nick Isiekwe(Saracens), Maro Itoje (Saracens), George Kruis (Saracens), Courtney Lawes (Northampton), Joe Launchbury (Wasps), Zach Mercer (Bath), Chris Robshaw (Harlequins), Sam Simmonds (Exeter), Sam Underhill (Bath
Front row: Lewis Boyce (Harlequins), Dan Cole (Leicester), Tom Dunn (Bath), Jamie George (Saracens), Dylan Hartley (Northampton), Alec Hepburn (Exeter), Kyle Sinckle, (Harlequins), Mako Vunipola (Saracens), Harry Williams (Exeter)
