The new season gets underway with the Bahrain Grand Prix on March 18-20 with the teams all participating in a three-day pre-season test at the same circuit from Thursday to Saturday this week.
Red Bull’s Verstappen is the reigning champion after picking up his maiden Drivers’ Championship in controversial circumstances in Abu Dhabi in December.
Mercedes still ruled triumphant in the Constructors’ Championship however as they took the team title for the eighth consecutive season, now trailing only Williams (nine) and Ferrari (16).
But though either Mercedes or Red Bull have won the driver and team titles for all of the last 12 years, Horner expects change in 2022.
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Still despite the increased threat of Ferrari and McLaren in particular, the Red Bull team principal predicts title-holder Verstappen and seven-time world champion Hamilton will be the two main protagonists of another thrilling season.
He told BBC Breakfast: “The rivalry between those two has been so intense. You might get a couple of other drivers come into that fray as well.
“It was epic last year. If that continues, there’s going to be some fantastic races in the season ahead. It’s fantastic.
“It’s great for the sport. The sport has never had so much coverage and such a following, it’s gone exponential over the last season and it’s great to see.
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“This is the biggest rule change in 40 years, it’s a clean sheet of paper. Not one single component carries over from last year, the tyres, the aerodynamics, everything is different.
Niels Wittich and Eduardo Freitas will replace Masi and will alternate in the role while Herbie Blash will operate as a senior advisor, having previously been the deputy race director to Charlie Whiting.
Horner added: “It’s going to be interesting to see how that works. For me it’s never ideal to have… you want consistency. Having one race director for me was preferential to splitting that role.
“We have a new president who has come in and inherited that situation and he’s looked to impose change.
“It’s great that Herbie Blash, very experienced race control member, is coming back into the fray as well. We’ll see how it pans out.
“I thought it was harsh on Michael Masi that he was replaced after a lot of pressure being put on him. Everything his back to zero. New season, new regulations, everything to play for.”