Owen Farrell has been retained as England captain for the Six Nations but there are several big-name casualties in the training squad named for the opener against Scotland on 5 February.
George Ford continues to miss out despite his outstanding form at the heart of Leicester's revival with Farrell, Marcus Smith and uncapped Bath prospect Orlando Bailey included as fly-halves.
There is no place for versatile back Elliot Daly despite his recovery from the stress fracture that forced him to sit out a successful autumn, and his Saracens colleagues Mako and Billy Vunipola also remain in international exile.
A fifth ever-present from the 2019 World Cup squad, and up until now a key member of Eddie Jones' back row, has been frozen out in flanker Sam Underhill.
The uncapped Bailey, Alfie Barbeary, Ollie Chessum, Tommy Freeman, Ollie Hassell-Collins and Luke Northmore continue Jones' overhaul of his England squad as he builds for France 2023.
Ireland will visit Twickenham on 12 March to face the English in round four of the Six Nations.
England squad
Backs: Mark Atkinson (Gloucester Rugby), Orlando Bailey (Bath Rugby), Owen Farrell (Saracens), Tommy Freeman (Northampton Saints), George Furbank (Northampton Saints), Ollie Hassell-Collins (London Irish), Max Malins (Saracens), Joe Marchant (Harlequins), Jonny May (Gloucester Rugby), Luke Northmore (Harlequins), Jack Nowell (Exeter Chiefs), Raffi Quirke (Sale Sharks), Harry Randall (Bristol Bears), Henry Slade (Exeter Chiefs), Marcus Smith (Harlequins), Freddie Steward (Leicester Tigers), Ben Youngs (Leicester Tigers).
Forwards: Alfie Barbeary (Wasps), Jamie Blamire (Newcastle Falcons), Ollie Chessum (Leicester Tigers), Luke Cowan-Dickie (Exeter Chiefs), Tom Curry (Sale Sharks), Alex Dombrandt (Harlequins), Charlie Ewels (Bath Rugby), Ellis Genge (Leicester Tigers), Jamie George (Saracens), Joe Heyes (Leicester Tigers), Jonny Hill (Exeter Chiefs), Maro Itoje (Saracens), Courtney Lawes (Northampton Saints), Lewis Ludlam (Northampton Saints), Joe Marler (Harlequins), Bevan Rodd (Sale Sharks), Sam Simmonds (Exeter Chiefs), Kyle Sinckler (Bristol Bears), Will Stuart (Bath Rugby).