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Manning opened the game with a 12-play, 71-yard drive and beat a Philly blitz to hit Anthony Gonzalez in the corner of the end zone for a 3-yard TD.
After Manning fumbled deep in his own territory, Dwight Freeney swatted the ball away from McNabb and Indy's Keyunta Dawson recovered.
Manning took advantage right away, finding Wayne down the left sideline on the next play. Wayne scooted down the sideline, then made a nifty inside cut near the 10-yard line to avoid a defender for a 76-yard TD to give Indy a 14-0 lead.
The Colts made it 17-7 when Shane Andrus made a 24-yard field goal late in the first half and added two more field goals by Andrus in the second half.
Philadelphia didn't score again until Adam DiMichele hooked up with Brandon Gibson on a 21-yard TD pass with 26 seconds to go.
"I don't think anybody offensively was really happy with what happened last week. It started with me and the entire offensive starting unit," Manning said. "Overall I thought everybody came back and did a better job tonight."
NOTES: Manning was presented with his third MVP trophy at halftime. ... McNabb was 5 of 7 for 77 yards with one touchdown. ... There were no protests outside the stadium regarding Vick, though a few fans brought in signs to express concerns about last week's signing. ... Colts S Matt Giordano left with a groin injury, RB Mike Hart hurt his ankle and RB Chad Simpson departed with a left shoulder injury. ... Philadelphia CB Ellis Hobbs injured his left ankle.
[Associated Press;
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