But the coronavirus will cast a shadow over the show.
With less than four weeks until Election Day, the pandemic’s presence looms larger than ever over the nation, and the political fortunes of incumbent President Donald Trump and his rival, former Vice President Joe Biden.
More than 211,000 people in the U.S. have died from Covid-19 this year, and millions more have lost their livelihoods amid pandemic shutdowns and economic stagnation.
Those infected include Trump, 74, who revealed on Friday that he and first lady Melania Trump had tested positive for coronavirus after he spent months downplaying the severity of the deadly virus.
Trump was hospitalized the next three days at Walter Reed medical center undergoing aggressive treatment. During that same 72 hours, more than a dozen White House aides and Republican lawmakers announced they, too, had tested positive for the virus.
Pence and Harris will take the stage just two days after Trump was discharged from the hospital and into the care of White House physicians. Pence has tested negative for the virus, but as a precaution, he and Harris will be more than 12 feet apart and separated by plexiglass.
The 90-minute debate will be held in Kingsbury Hall at the University of Utah, starting at 9 p.m. ET. The event will be livestreamed on CNBC.com and will air on White House pool networks.
Here’s what Pence and Harris each need to do:
Pence has to shine in the spotlight
The president’s hospitalization has drastically changed the dynamic of the debate, said Mitchell McKinney, director of the Political Communication Institute at the University of Missouri and an expert on presidential debating.
“Like many people, I initially thought most of the attention Wednesday would be focused on Harris, but in the past week so much has changed with the president in the hospital,” McKinney told CNBC on Tuesday.
“Voters are looking at Mike Pence now with a new sense of urgency.”
Biden’s age — 77 — had been a frequent target of the Trump campaign, which has been openly been making claims about his mental acuity and health. But Trump’s diagnosis, and the urgent questions about his condition, have put more pressure on Pence to display his readiness to lead.
“Both of the presidential candidates are old, and they have health issues,” said Aaron Kall, director of the University of Michigan’s debate program.
“So are these [vice presidential] nominees ready to step in at a moment’s notice? Are they experienced? Do they have a good temperament?” Kall said. “Voters at the debate are really going to be asking those questions, given the health of the two people at the top.”
Harris needs to tie Pence to Trump’s worst excesses
Harris may be debating Pence, but she should train her sights on Trump, as well, McKinney said.
“Harris has to call into question the entire Trump operation, all the chaos. She’ll take it to Mike Pence, but the case she’s prosecuting is the case against Trump,” he said.
Pence has been among Trump’s most loyal and outspoken defenders throughout his tumultuous first term. As a longtime public figure and a former talk-radio host, he’s good at the sort of verbal jousting required in a debate. Pence scored a clear victory over then-Democratic nominee Hillary Clinton’s running mate, Sen. Tim Kaine, in their debate in 2016, polls showed.
But he may be forced to play defense against Harris, a former prosecutor, who showed in the Democratic primary that she was willing to go on the attack.
“There’s a gendered element here. It’s typically the female candidate who will bring the most aggression to the stage to show she’s up for it,” McKinney said.
“The expectation is on her to pick apart this rosy picture Pence wants us all to imagine.”
Pence can take advantage of the format
With Trump away from the campaign trail, Pence is being forced to pick up the slack — an enormous task given recent polls showing Biden’s lead over the president creeping into the double digits in nationwide polls.
The format of Wednesday night’s debate is likely to work in Pence’s favor, however.
“The vice presidential debate has always been more of a discussion and less of a podium battle than the top of the ticket debates,” McKinney said. “This works in Pence’s favor, because that’s his style.”
Hewing to VP debate tradition, Pence and Harris will be seated at tables on Wednesday night.
The Commission on Presidential Debates, as part of its slate of virus-related adjustments, will seat the two contenders more than 12 feet apart. There will be no handshake between the candidates, or with the moderator, USA Today’s Susan Page.
The commission also announced this week that there will be a plexiglass wall between them — a decision that reportedly prompted Pence’s team to raise objections.
On Wednesday night, Pence needs to reassure voters that the chaos engulfing the White House is temporary, McKinney said.
Harris doesn’t need to defend her record
In the Democratic primary debates last year, Harris was tripped up by Hawaii Rep. Tulsi Gabbard, who zeroed in on Harris’ record as a former prosecutor.
Pence might take a similar tack, by contrasting the California senator’s record with the Biden campaign platform she now supports.
Harris should keep herself out of that position, Kall said.
“She really doesn’t have to defend her record,” Kall said. As Biden’s running mate, her job “is to support the person at the top of the ticket. So her position is the position of Joe Biden.”
Pence should deliver the ‘Trojan Horse’
Numerous speakers at last month’s Republican National Convention, including Pence and Trump, portrayed Biden as a “Trojan horse” — that is, a politically milquetoast vehicle through which far-left Democrats can smuggle radically progressive policies.
If Pence wields that message effectively in the debate, he might land a strong blow against Harris, by suggesting to on-the-fence viewers that Biden’s younger, more liberal running mate would really be running the show.
“It’s easier to do that than attack Biden directly,” Kall said. “In some ways, Biden has proved Teflon.”
The usual attack labels, which often stick to Democratic politicians – “socialist,” “radical,” “far-left” – seem to be bouncing off Biden.
But “those can be pinned on her a lot more easily,” Kall said of Harris, and “they’re much more likely to be impactful.”