Current TB vaccines are flawed and will fail to protect people living near the Equator, warn UK experts.
TB is caused by Mycobacterium tuberculosis
While boosting a person's natural immunity works in richer Western countries, in poorer nations this approach does not work, they say.
According to the University College London team, a better way would be to suppress inappropriate responses by the body that allow the disease to thrive.
They put forward their argument in Nature Review Immunology.
However, their investigations are at a very early stage and the theory has not been proved in humans.
TB is a big problem globally. It is killing at least two million people a year, or 5,000 every day, mainly in the developing world.
Three or four people get the disease every second, meaning about nine million new cases develop every year.
In the UK there are about 7,000 cases every year and nearly half of those are in London.
The current vaccine used for TB - the BCG - appears to work in Western nations.
However, in countries nearer the Equator, such as Asia, Africa and Latin America, it is failing, claim Professor Graham Rook and his team.
Vaccines generally work by exposing the body to a very small, but harmless amount of the agent that causes the disease so the body can learn to attack it and prevent future disease.
With TB, it is not that simple, said Professor Rook who has been investigating the disease with funding from the British Lung Foundation.
"We think that hundreds of millions of dollars are going to be spent testing new vaccine candidates and we think they are going to fail in exactly the same places and for exactly the same reasons as the BCG vaccine has failed.
"People in developing countries already have the protective mechanism because they encounter large numbers of organisms closely related to TB in their environment.
"The reason they get TB does not seem to be that they lack the protective mechanism but rather that they have simultaneously another mechanism that acts in a subversive role to undermine the effects of the protective mechanism."
This subversive mechanism allows TB to evade destruction by the immune system and thrive in parts of the body such as the lung.
"What we need is a new kind of approach to vaccination - rather than turn on the protective mechanism, one needs to turn off the mechanism that is having these subversive effects."
"We think this is possible," he said, adding that scientists in the UK, Spain and Brazil were working on candidates that appear to do this in animals.
He said these vaccines could be given alongside regular TB vaccines to boost protection and might also be good as treatments in people who already have TB.
Professor Douglas Lowrie from the National Institute of Medical Research in the UK has developed a candidate DNA vaccine that turns off the subversive TB response.
He said he was hoping to test the vaccine in humans, but warned it could be many years before results were available.
He said it also appeared to treat animals that already had TB and that this response was being explored by other scientists in humans.
Professor Peter Davies, secretary of TB Alert, said: "It's very interesting and a good idea but we need to show this in practice.
"Quite often the theory looks good but it does not stand up."
He said it was worth developing these test vaccines to see if they work, but added that current vaccine development should also be continued and used in parallel.