The storm is forecast to strike most of the eastern coast Wednesday into Thursday, and several feet of snow and heavy ice could result in power outages throughout the region.
The cities of Boston and New York could see as much as a foot of snow, while parts of the Tri-State area could see up to 16 inches.
The storm system is moving out the Rockies through Tuesday, bringing snow into the Southern Plains before meeting cooler air further east.
Freezing rain will fall along I-80 and in the mountains of Virginia, with ice accumulation of more than a quarter-inch possible in Roanoke, Charlottesville, west to Beckley, West Virginia.
Lighter snow accumulations from Indiana to New Hampshire are expected by Wednesday, WPC said.
Blustery wind conditions will also be a concern, with some areas, especially along the coast, coming close to blizzard conditions. Sustained winds of 25 to 35 mph are possible, with gusts as high as 45 mph at times.
Shippers have contingency plans for vaccine distribution
The weather could make travel very difficult or even impossible in some areas, the National Weather Service said.
The winter snowstorm will hit parts of the mid-Atlantic into New England beginning Wednesday, when shippers are scheduled to make 66 deliveries nationwide. Later in the week, other vaccines will be shipped in Pfizer’s distribution boxes requiring dry ice.
FedEx doesn’t expect any “significant impact” to service, the company’s spokeswoman Shannon Davis wrote in an email Monday, adding that they will continue to monitor the forecast.
“We have a team of 15 meteorologists monitoring conditions 24/7, and we have contingency plans in place should we see any severe weather,” she said.
UPS didn’t immediately respond to CNN’s request for comment, but also has an in-house team that monitors the weather.
Operation Warp Speed’s Gen. Gustave Perna told reporters Monday that his group plans for many different issues, with the worst case scenario being an accident of a delivery vehicle or aircraft. Bad weather falls in the middle of the spectrum of problems, he said.
Some doses will be held in a “safety stock” should there be an issue.
CNN’s Steve Almasy, Judson Jones, Melissa Nord and Taylor Ward contributed to this report.