That would make for an amusing ending.
The American Marines storm Rome, kill the emperor declare themselves to be the new leaders
And then die of smallpox infections.
Sounds like an outer limits episode.
Developing an actual vaccine would probably be beyond their capacity, at least initially, but no doubt one or more of the Marines would know about inocculation, which probably reduces the mortality rate by 90%+.
Anywho, it does not appear smallpox was present in the Roman Empire, at least none of the Greek or Roman medical writers describe this highly describable disease.
The most common theory is that Arabs brought smallpox to Europe in the 7th or 8th centuries.
I also believe Marines, at least those posted to 3rd-world toilets, are vaccinated against every damn thing there is.