People could have an immunity to vCJD and similar diseases after persistent exposure to milder strains of the agent that causes them, scientists suggest.
Diseases like vCJD affect the brain
Experts at Yale University and Nagasaki University medical schools carried out studies on cells.
Writing in Science magazine, they said regular doses of the weaker infection appeared to offer protection.
A UK expert said further understanding of how the effect works could lead to a preventative therapy being developed.
It might also help to explain why fewer people than predicted have died from vCJD.
The US and Japanese researchers also put forward the theory that the diseases are caused by viruses.
Misfolded proteins called prions are present in brain and nerve tissue infected with vCJD, and related diseases known as transmissible spongiform encephalopathies (TSEs).
Other TSEs include classic CJD, BSE, which infects cattle, and scrapie, which infects sheep.
But there is doubt as to whether prions are the cause of these diseases, or simply the result of them.
Earlier research on animals showed a weaker strain of CJD appeared to offer protection against a more destructive strain.
In this study, the scientists looked at the effects of various prion diseases on mouse brain cells.
It was found that cell cultures infected with a weak strain of CJD were protected from infection by two strains of sheep scrapie agent.
One of these sheep strains, in turn, also appeared to protect against a virulent CJD strain.
In addition, the presence of a weak CJD strain protected cells from infection by a more virulent and potentially lethal form.
The researchers also found that the protective effect did not involve cells from the immune system.
Professor Laura Manuelidis, of Yale University, said: "This gives us much more of an idea of what to target".
vCJD first emerged in 1995 and has since claimed 151 lives in the UK.
The disease is believed to have passed from cattle to humans through meat infected with the disease BSE.
Although there is ongoing research into potential treatments, there is currently no cure for the disease.
Scientists warn that incubation periods may vary according to people's genetic make-up and there may be many more cases to come.
However many experts believe the epidemic has peaked.
The American and Japanese researchers behind this latest research suggest the reason for this relatively small number of cases might be that large sections of the population are protected by the exposure to weaker strains of TSEs.
They suggest a virus may be the actual cause of such diseases.
Professor Manuelidis said: "This, as well as our previous results showing that most of the abnormal prion protein can be separated from infectious particles, point to a virus as the causal agent."
She added: "These results are not consistent with the idea that abnormal forms of the prion protein are infectious."
Dr Stephen Dealler, a consultant medical microbiologist at the Royal Lancaster Infirmary, said the study's findings were extremely interesting.
"It has been suggested that maybe we've all been infected already with scrapie and that's why we have not seen more cases of vCJD.
He added: "The most important thing is that this is a first step on the way to working out why the protective effect occurs, and then being able to design a therapy - something like a vaccine.
"It wouldn't be a vaccine, but a way to protect someone against further infection.
"It would be quite remarkable if that could be done."
CJD expert Professor Hugh Pennington, of Aberdeen University, said the study was interesting.
But he added:" It's a big step to extrapolate it to apply it to the human situation."