Scrum-half Natasha Hunt is one of several key England players returning from injury for Saturday's Women's Six Nations trip to Ireland.
There are seven changes to the side that beat Wales, with Claudia MacDonald back on the wing.
Having made their injury return as replacements last week, props Hannah Botterman and Maud Muir start in Cork.
Backs Helena Rowland and Amber Reed are also poised to rejoin the Test arena, included on the bench.
Hooker Amy Cokayne will miss the rest of the tournament with a calf injury, meaning Connie Powell is between Botterman and Muir in an all-new front row.
Full-back Ellie Kildunne joins MacDonald and Abby Dow in the back three, with Jess Breach dropping out of the matchday squad.
Sarah Beckett, usually a back row, starts at lock alongside Gloucester-Hartpury team-mate Zoe Aldcroft.
Hunt 'looking forward'
Hunt last played for England in September 2022 before being a shock exclusion from the World Cup squad.
The fast and unpredictable style of play that seemed to cost her the trip to New Zealand may now be prized by an England team looking to make more use of its talented backs.
One such back is Rowland - a star of England's World Cup campaign until a foot and ankle injury meant she had to miss the final defeat by New Zealand.
Middleton said Hunt "will be delighted" to return to England duty, adding: "Mo [Hunt] has made it absolutely clear that all she wants to do is look forward. That's the best way for all of us.
"She is a real jack-in-the-box. She gets to the ruck and looks for every option that is possibly on. She plays a real high-tempo game.
"Coming back from the World Cup you always look at how you potentially want to evolve your play. How we have started to evolve the side definitely opens that door back up for Mo."
England are seeking a fifth successive Six Nations title and victory would set them on course for a Grand Slam-deciding game against France in front of a record crowd at Twickenham.
The Red Roses have won all of their matches so far by 50 points and struggling Ireland, who have lost their opening three games, may be their easiest task yet.
Middleton acknowledged Ireland are in "a period of transition" and ominously added: "We'll play flat out. There are players who haven't played for quite a while, there are players who are fighting to keep the shirt.
"There is a massive goal at the end of this tournament, everybody wants to be involved as much as they can. There will be no quarter given."
England: Kildunne; Dow, Tuima, Heard, MacDonald; Aitchison, Hunt; Botterman, Powell, Muir, Aldcroft, Beckett, Kabeya, M Packer (capt), Matthews.
Replacements: Davies, Carson, Bern, Burns, Talling, L Packer, Reed, Rowland.