Full-back Emma Sing will make her first start for England in Saturday's Women's Six Nations match against Wales.
The Red Roses welcome back four players from injury for their toughest challenge of the tournament so far at a sold-out Cardiff Arms Park.
Alex Matthews returns at number eight, while props Hannah Botterman and Maud Muir and back Ellie Kildunne are among the replacements.
Hooker May Campbell is set to make her debut off the bench.
England had 19 players unavailable for their round-two demolition of Italy, but are slowly returning to full strength before the likely tournament decider against France on 29 April.
Matthews comes in at number eight as Middleton continues to seek a replacement for retired former captain Sarah Hunter.
Zoe Aldcroft - number eight last week - returns to the second row, while Lark Davies starts at hooker as Amy Cokayne is playing for the Royal Air Force team on Saturday.
After Claudia MacDonald was injured against Italy, Abby Dow moves on to the wing and 22-year-old Sing, who has four England caps, fills in at 15.
Red Roses head coach Simon Middleton says Gloucester-Hartpury's Sing is "a different type of full-back".
"She's got a really rounded skillset," he added.
"She's a great kicker. She kicks off the tee probably further than anyone else in the women's game. She kicks out of hand really well.
"She's a great carrier of the ball as well and she's great under the high ball."
England cannot 'overpower' professional Wales
England have dominated the Six Nations since becoming professional in 2019 and are seeking their fifth successive title.
Wales are a team on the rise after players received contracts for the first time in January 2022 and are second behind England in the table with two wins from two games.
Middleton said Wales are "where you'd expect and hope they'd be 18 months into contracts".
"Full-time isn't a quick fix; it takes time to embed," he explained.
"You can see the massive benefit of that now. They will have confidence on their own turf with a massive crowd behind them.
"As a team they feel very together, very connected and very strong. Whereas before we have been able to overpower them, like we have with a lot of teams because of the physical thing that comes with full-time contracts, that won't be there to the extent that it has been previously.
"It will be an ongoing arm-wrestle, which is great because then it comes down to tactics."
England team
England: Sing; Breach, Tuima, Heard, Dow; Aitchison, L Packer; Carson, Davies, Bern, Aldcroft, O'Donnell, Kabeya, M Packer (capt), Matthews.
Replacements: Campbell, Botterman, Muir, Burns, Beckett, Wyrwas, McKenna, Kildunne.