The boys in black, green and gold came out strong and continued to dominate throughout the first 35 but frustratingly only led by a score at the break as Rotimi Segun, a Saint in England colours, answered Jacob Conner and Harry Mallinder's scores.
The second half started in a similar fashion to the first, Lewis Ludlam adding Saints' third before England hauled themselves level with two more tries of their own, including one for Saintsman Paddy McDuell, only for Manley to snatch victory in the final play.
It was welcome relief for the visitors who might well have been left ruing scoring just the once during an intense opening half hour of pressure. England manned the barricades by any means necessary to keep them at bay and it took until the 29th minute for a string of penalty offences to be punished, a driving maul taking Conner over.
Despite having had their backs to the wall for the best part of half an hour England quickly responded through a familiar face, Segun producing a typically powerful and pacy break to outstrip his clubmates and level up the tie.
There was still time for the lead to swing back onto Saints' side however and when Mallinder forced his way between defenders and under the posts, he also converted for a 5-12 advantage at the break.
Just 10 minutes after the sides re-emerged, the game looked to have taken a sizeable swing in Saints' favour - another power drive finished off by Ludlam - but in the space of six minutes the home side surged back into the tie with a pair of scores including fly half McDuell's effort.
Both sides had their chances as the game wound down but just like in the first half it was the Saints, through Manley, who would have the late and final say.
Elsewhere on Sunday, fly half Sam Olver started as England Under-18 put on an impressive display in sweeping Wales aside 44-7 in Swansea. Jordan Onojaife was also involved.
10mins SAINTS Miss pen Mallinder
29mins SAINTS Try Conner 0-5
30mins ENGLAND Try Segun 5-5
35mins SAINTS Try and Con Mallinder 5-12
HALF-TIME ENGLAND 5 SAINTS 12
45mins SAINTS Try Ludlam 5-17
51mins ENGLAND Try 10-17
57mins ENGLAND Try and Con McDuell 17-17
70mins SAINTS Try Manley 17-22
FULL-TIME ENGLAND 17 SAINTS 22