The city has more than one million people and is 80 miles from the area where the first case broke out this month.
There are now 17 confirmed cases of Ebola in this current outbreak.
This includes one death, 21 probable cases and five suspected ones.
The World Health Organisation (WHO) has not declared the outbreak a global health emergency but said the risk of spread within Congo is “very high”.
A WHO spokesman said: “The confirmed case in Mbandaka, a large urban centre located on major national and international river, road and domestic air routes increases the risk of spread within the Democratic Republic of the Congo and to neighbouring countries.”
Nine neighbouring countries are also at high risk of the virus breaking out there, according to officials.
Vaccinations are expected to start early in the week.
A major challenge will be keeping the vaccines in cold in the impoverished country with poor infrastructure.
The first batch of experimental vaccines are due to be used next week with 4,000 shots sent by the WHO to capital city Kinshasa on Wednesday.
The vaccine, VSV Ebola Vaccine and developed by Merck, is still not licensed, but proved effective in the 2014 outbreak of the virus.
Speaking of the new medicine, John Edmunds, professor of infectious disease modelling at the London School of Hygiene and Tropical Medicine, said: “Officially it has to be part of some sort of research study because it’s not a licensed vaccine but there is a work-around so you can use it under special circumstances.
“They won’t be randomising people – everyone who needs it will get it. “It’s a big headache to deliver the vaccine and keep it frozen. It is a major operation to get the cold chain up and running and to get it right out into the field.”
Ebola is spread through direct contact with bodily fluids, including blood, sweat and spittle.
The disease takes between two and three days to develop once someone has been infected. Symptoms include vomiting, diarrhoea, decreased liver and kidney function and in extreme cases, internal and external bleeding.
The Democratic Republic of Congo has witnessed nine outbreaks of Ebola since 1976.
The threat echoes the West African Ebola crisis of 2014, which infected over 11,000 people and spread to countries such as Guinea, Sierra Leone and Liberia across a two-year period.