Ramirez is a first-year starter at center after injuries sidelined J.D. Walton and Dan Koppen and Vasquez is set to make his first career start at right guard in place of Orlando Franklin when the Denver Broncos (6-0) take on the Indianapolis Colts (4-2).
Vasquez slid over when Franklin sprained his left knee and ankle in a pileup in the end zone against Jacksonville last week. That marked the first time Vasquez ever played at right tackle, although he filled in occasionally at left tackle in college.
Although all 60 of his NFL starts have come at guard, Vasquez took plenty of snaps in Franklin's spot last summer for this very scenario.
''Yeah, he's a big, physical guy. He's got long arms. He's athletic,'' coach John Fox said of the 6-foot-5, 335-pounder who will have his enormous hands full against Colts pass-rusher Robert Mathis.
Chris Kuper, whose career has been sidetracked by surgeries that left a jigsaw scar on his left ankle, filled in at right guard when Franklin went out, and the Broncos put together two drives that ended with Knowshon Moreno TD runs behind the makeshift line.
Offensive coordinator Adam Gase said the challenge facing Vasquez is he'll be blocking defenders ''that are a lot smaller and a lot faster. When you're inside you can get your hands on them a lot quicker.''
With journeyman Chris Clark his capable blindside defender ever since All-Pro left tackle Ryan Clady went on IR with a foot injury a month ago, Manning has been sacked just twice.
Add the three sacks he took in the opener, and Manning has been sacked fewer times than any NFL quarterback who's started all of his team's games.
He realizes many of his old teammates would love to knock him down in his return.
''That's something, if I could avoid, I'd be in favor of it,'' Manning said, ''but it would be a challenge. Like I said, we finished the game against Jacksonville with our right guard playing tackle. Our starting left tackle has been out for the season and we're playing in one of the loudest places to play, if not the loudest, against a great pass-rush team. We've got a great challenge from that standpoint.''
Nobody has a bigger task than Vasquez, who declined to comment Friday when approached at his locker. However, he told Denver radio station 104.3 The Fan one day earlier than all his cross-training at right tackle last summer helped prepare him for this moment.
The Broncos are averaging 44 points a game, but Manning notes the offense is still a work in progress because he's still getting used to some of his new teammates and working behind his makeshift O-line.
''We got a lot of guys that are playing for the first time. We got a first-year center. Last week we finished the game with the right guard playing right tackle, so there's a lot on my plate from that standpoint and a lot on our team's plate that we still need to improve on,'' Manning said.
Notes: MLB Wesley Woodyard (shoulder stinger) was limited all week, but he insisted, ''I'm playing Sunday.'' He missed last week's game after getting hurt at Dallas. ... Franklin missed practice all week but didn't have his walking boot Friday in the locker room.
AP NFL website: www.pro32.ap.org
Follow AP Pro Football Writer Arnie Melendrez Stapleton on Twitter: http://twitter.com/arniestapleton
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