Hamburg - An early tuberculosis vaccine dating back to the 1920s has been vastly improved thanks to genetic engineering technology, according to a team of German researchers.

The new discovery by the scientists from the Max Planck Institute for Infection Biology offers new hope for the many TB patients - especially HIV/AIDS patients - who are often unresponsive to the old vaccine.

The newly developed vaccine, VPM1002, is based on the Bacillus Calmette-Guerin (BCG) vaccine, which was created in 1921. BCG is the most commonly used tuberculosis vaccine worldwide but is now frequently ineffective. The promising new vaccine has reached the clinical trials stage and, it is hoped, will be ready for worldwide use in the next 10 years.

Tuberculosis is a disease that primarily affects the lungs. It is transmitted easily when people live in very close proximity to one another, and is widespread in developing countries. According to the World Health Organization, nearly one third of the world's population has been exposed to the tuberculosis pathogen; approximately 8 million people contract the illness and 2 million people die of it every year.

Most people who contract TB do not develop full-blown symptoms. Some 90 per cent of people who have been exposed to the pathogen experience that is known as a latent infection. However, one in 10 of these latent infections progress to the active form of the disease, and people who are not treated have only a 50 per cent chance of survival. TB is the leading cause of death among people infected with HIV.

TB treatment includes isolation (to break the chain of transmission) and therapy with several types of antibiotics over the course of at least six months. Resistance to antibiotics is a growing concern, and the increasing occurrence of multi-drug-resistance has been quite alarming.

Vaccination programmes are pivotal for prevention, and the development of new and more effective vaccines is of ever-increasing importance.

Professor Stefan Kaufmann, Director of Germany's Max Planck Institute for Infection Biology, led the team of researchers that genetically modified the BCG to create VPM1002.

"The weakened vaccine was genetically modified in such a way to ensure that it is no longer able to hide from the human immune system and even stimulates the body's own defences," explains Leander Grode, who now heads the project at Vakzine Projekt Management GmbH (VPM). To make this happen, a gene from a different bacterium, Listeria, was inserted into the vaccine.

In the new scenario, the vaccine bacteria are taken up by the scavenger cells of the human immune system (macrophages) and end up in their digestion chambers, called phagosomes. The genetically engineered modification allows the vaccine bacteria to escape from the phagosomes. They are then present in the middle of the immune cell.

Dr Grode explains, "This alarms the rest of the immune system, which is then armed to repel real tuberculosis pathogens."

VPM1002 stimulates the human immune system to prevent infection by the most common TB pathogen, Mycobacterium tuberculosis.

The vaccine has proven successful in animal models, and human trials are now underway. Testing the vaccine for safety and long-term effects will take up to 10 years, according to a statement from the institute.

The basic research for VPM1002 was undertaken by Professor Kaufmann's team at the Max Planck Institute. The vaccine was licensed to VPN, a public-private partnership between the German Federal Ministry for Education and Research and the Helmholtz Centre for Infection Research, in 2004.