Both vice presidential nominees are seasoned debaters. During her ill-fated presidential primary bid, Harris participated in several debates and made headlines for her zingers, including a clash with Biden over busing to integrate schools. Expectations are high for her in the matchup against Pence, who hasn’t participated in a debate since 2016 but has held his own ground in the past.

In an interview with Hillary Clinton for her podcast “You and me Both,” Harris spoke about the challenges of preparing the debate, including her expectation that Pence could offer “a series of untruths” from the debate stage.

“I don't necessarily want to be the fact checker,” Harris said in the interview. “At the same time, you know, depending on how far he goes with whatever he does, he’s going to have to be accountable for what he says.”

Pence has called Harris a “skilled debater” and has told supporters at campaign events that he looks forward to being on stage with her, though he has remained mostly tight lipped about his expectations or how he’s been preparing for the matchup.

In 2016, Pence participated in the vice presidential debate against Sen. Tim Kaine and was seen to have successfully thwarted attacks over comments Trump made about women and Mexican immigrants, as well as his policy proposals.

During his debate against Kaine, Pence was disciplined, poised and polished and largely waited for his turn to get a response in.

-ABC News' Justin Gomez and Averi Harper

Two, five-foot tall plexiglass walls will stand between Vice President Mike Pence and Sen. Kamala Harris at Wednesday night’s debate.

The thick plastic barriers, approved by the Commission on Presidential Debates, will try to prevent the possible transmission of the coronavirus as Pence and Harris face off onstage for 90 minutes.

The Debate Commission said the plexiglass was part of a “variety of health safety protocols,” according to a factsheet. “Plexiglass will be used as part of the CPD’s overall approach to health and safety.”

Experts say that among the many protective measures put in place, the proposed plexiglass may not be the most effective option, particularly in light of updates from the Centers for Disease Control and Prevention to its guidelines on Monday acknowledging the potential for airborne transmission of the virus while indoors.

According to the CDC, it's possible for the virus to be transmitted beyond 6 feet by forming particles that can linger in the air for prolonged periods of time when infectious individuals “cough, sneeze, sing, talk, or breathe." The risk of airborne transmission is greatest in poorly ventilated indoor spaces as well as during prolonged exposure. Pence and Harris will be 12 feet apart from each other and from the moderator.

The clear dividers on stage could offer an added layer of protection, but it should not be a standalone measure, experts say.

More on experts concerns about safety protocols for the debate can be found here.

-ABC News' Sasha Pezenik and Ramie Fathy

Amid the controversy surrounding a plexiglass barrier at the vice presidential debate Wednesday, a number of Senate debates across the country have utilized the measures.

In last Friday's South Carolina debate, Democratic challenger Jaime Harrison brought his own plexiglass divider to his debate against Sen. Lindsey Graham.

Both candidates said they tested negative the day before the debate and those attending had to fill out a questionnaire saying they had no symptoms.

The Arizona Senate debate on Tuesday night also saw the candidates using plexiglass dividers.

In Colorado, Sen. Cory Gardner and Democratic challenger John Hickenlooper were separated with plexiglass dividers. Both candidates tested negative prior to the debate.

In North Carolina's debate last Thursday, plexiglass wasn't used, but Sen. Thom Tillis and challenger Cal Cunningham were socially distanced from each other and the moderator.

In Iowa, Theresa Greenfield and Sen. Joni Ernst shared a table with the moderators. All were separated by plexiglass barriers.

-ABC News' Meg Cunningham and Kendall Karson

Women's rights and advocacy organizations on the left have been working together to promote Harris's candidacy. This week they are gearing up too against what they fear will be sexist or otherwise biased attacks during the vice presidential debate Wednesday.

The long list of organizations, including BlackPAC, Color of Change PAC, EMILY's List WOMEN VOTE!, Planned Parenthood Votes! and UltraViolet say they are working in tandem on messaging and outreach. On the phone with ABC News, Shaunna Thomas, the head of UltraViolet, argued that female politicians are still more likely to face attacks -- subtle as they may be -- about their qualifications, trustworthiness and character. She said the coalition was planning to release content on social media and around neighborhoods Wednesday with an eye toward women of color in battleground states.

They want to underscore again the historic nature of the ticket.

"A lot of people are excited about this long overdue and historic moment for women of color and the whole country. Never has a woman of color served in such a position ... and it's time," she said.

The coordinated push comes as Biden again leaned into the issue of race and inequity in America on Tuesday during his event in Gettysburg, Pennsylvania.

"I think about what it takes for a Black person to love America that has a deep love for this country that has -- for far too long -- never been recognized," he said on the historic Civil War battlefield after talking about his conversations with the families of Black Americans whose loved ones have been killed by police.

-ABC News' MaryAlice Parks

Moderator Susan Page posed the first question to Harris, revealing the first of nine topics: The coronavirus pandemic.

Noting the president's recent diagnosis, Page asked Harris, "What would a Biden administration do in January and February that a Trump administration wouldn't do?"

True to her form as a prosecutor, Harris -- the first Black woman and first Indian American to take a vice presidential debate stage -- laid out her facts, arguing the administration knew about the threat of the virus in January but didn't act soon enough.

"They were informed that it's lethal in consequence, that it's airborne, that it will affect young people," Harris said. "They knew what was happening and they didn't tell you."

Harris then said the Trump administration still doesn't have a plan.

"Well, Joe Biden does and our plan is about what we need to do around a national strategy for contact tracing, for testing, for administration of the vaccine, and making sure that it will be free for all," she said.

There was no handshake between candidates -- customary at the top of such events -- due to COVID-19 precautions. The audience, limited to under 100 attendees, applauded Pence and Harris as they took the stage.

Former Democratic 2020 presidential candidate Pete Buttigieg, who played Pence at some mock debate rehearsals for Harris, was also spotted in the audience.