In-form Wasps back row Alfie Barbeary is one of six uncapped players in England's 36-man Six Nations squad.
The 21-year-old has scored four tries in seven games for his club this season after returning from injury.
Bath fly-half Orlando Bailey, 20, and London Irish full-back Ollie Hassell-Collins, 23, are also included.
Centre Manu Tuilagi, yet to make his comeback from a hamstring problem, and back row Sam Underhill - who hasn't played since December - are left out.
However captain Owen Farrell is included despite not playing since suffering an ankle injury in the win against Australia in November.
Fellow Saracens player Jamie George is one of the hookers - having initially been left out of the Autumn Internationals squad - after he returned from a knee injury ahead of schedule.
But fly-half George Ford, who has steered Leicester to the top of the Premiership, and Saracens back Elliot Daly, who has been short of game time, are left out.
Mako and Billy Vunipola, mainstays of the team that reached the 2019 Rugby World Cup final, are omitted once again.
Harlequins centre Luke Northmore, Leicester forward Ollie Chessum and Northampton full-back Tommy Freeman complete the set of uncapped players.
England's Six Nations squad
Forwards
Alfie Barbeary, Jamie Blamire, Ollie Chessum, Luke Cowan-Dickie, Tom Curry, Alex Dombrandt, Charlie Ewels, Ellis Genge, Jamie George, Joe Heyes, Jonny Hill, Maro Itoje, Courtney Lawes, Lewis Ludlam, Joe Marler, Bevan Rodd, Sam Simmonds, Kyle Sinckler, Will Stuart
Backs
Mark Atkinson, Orlando Bailey, Owen Farrell, Tommy Freeman, George Furbank, Ollie Hassell-Collins, Max Malins, Joe Marchant, Jonny May, Luke Northmore, Jack Nowell, Raffi Quirke, Harry Randall, Henry Slade, Marcus Smith, Freddie Steward, Ben Youngs.
While head coach Eddie Jones said he was "hopeful" Bath's Underhill, who hasn't played since suffering a head injury against Gloucester on 26 December, would feature later in the Six Nations, he was less certain Tuilagi would feature in the tournament.
"He has had a wee setback," said Jones. "If we are 100% optimistic we would say yes, if we are realistic it is probably about a 50-50.
"Selecting this squad has been a difficult task, we've got plenty of good young players coming through and some of our more experienced are rediscovering their best form.
"We think this 36 for the first training week reflects a good balance of that experience and up-and-coming talent."
'An extraordinary ability to break tackles'
Barbeary has come up through England's age-group sides and captained the Under-18 teamBarbeary, who has converted from a hooker into the back row, is enjoying his longest spell of consistent club rugby after a couple of years hampered by injury.
"He has an extraordinary ability to break tackles and to carry the ball forward in close contact," said Jones.
"He feels his best position is in the back row. We agree and we are looking forward to seeing how quickly he can move forward into Test rugby."
Jones praised Bailey's versatility and fortitude for Premiership strugglers Bath and said 21-year-old Chessum is a possible long-term successor to Courtney Lawes in the squad.
"Orlando can take the ball to the line and is a strong defender who can play 10, 12 or 15," he said.
"We are particularly looking for those multi-skilled backs - players who are going to be important.
"Ollie Chessum is a young back-rower-cum-lock with good line-out skills.
"He can carry and hit, he has plenty of energy and vigour."