Simmonds wins a fourth cap at No 8 in the absence of injured duo Vunipola and Hughes.
Six Nations: Ben Te'o makes return as Eddie Jones names England side to face Italy
Centre Ben Te'o will play his first England Test for almost a year after overcoming injury to be included in the team named by Eddie Jones to face Italy in Rome in their opening Six Nations match on Sunday.
After featuring for the British and Irish Lions in New Zealand last summer, Te'o played only a handful of games for Worcester before suffering an ankle injury in October that required the insertion of a plate.
After extensive rehabilitation he has clearly done enough in the England camp to impress Jones, and will partner Owen Farrell on Sunday, winning his ninth England cap but making only his second start.
In the absence of injured duo Billy Vunipola and Nathan Hughes, Sam Simmonds wins a fourth cap at No 8, with Chris Robshaw and Courtney Lawes either side of him in the back row.
Mike Brown retains the fullback jersey, with Anthony Watson and Jonny May on the wings.
Uncapped prop Alec Hepburn was named among the replacements, as was wing Jack Nowell, who has recovered quicker than expected from an ankle injury, and usual first-choice centre Jonathan Joseph.
England have won all 23 of their previous meetings with Italy, averaging 40 points a game, though they had something of a scare at Twickenham last year when they struggled to deal with the Italians' surprise "no ruck" tactics before coming from behind at halftime to emerge 36-15 winners.
England, who have lost only one of their 23 games under Eddie Jones, are seeking to become the first team to win the Five/Six Nations championship outright three years in a row.