Borthwick has jettisoned three established performers under his predecessor Eddie Jones, who was sacked last month and has now been appointed Australia boss.
Number eight Vunipola and wings May and Nowell were all involved in the 27-13 defeat by South Africa that concluded the autumn and spelled the end of the Jones era.
Cole was dropped by England after the 2019 World Cup final while Daly has been frozen out since last year’s Championship despite his superb form for Saracens.
Northampton’s rookie fly-half Fin Smith is present for the first time, providing cover for Owen Farrell and Marcus Smithwhile Ollie Hassell-Collins, George McGuigan, Cadan Murley and Jack Walker are the other uncapped players.
“This is an exciting squad, with a blend of Six Nations experience and young talent, and includes players who are in excellent form in the Premiership,” said Borthwick.
“We are all looking forward to the challenges of the Six Nations and we will approach this great tournament with a spirit of courage and total commitment. I know the players can’t wait to get back to Twickenham and give our fans a performance they can be proud of.
“The hard work for the Scotland game starts now.”
George McGuigan (Gloucester Rugby, uncapped)
Jack Walker (Harlequins, uncapped)
Ollie Hassell-Collins (London Irish, uncapped)
Cadan Murley (Harlequins, uncapped)
Fin Smith (Northampton Saints, uncapped)
Jack van Poortvliet