Biomarker discovery offers hope for new TB vaccine development

12 Apr 2016
12 Apr 2016

A team of scientists from the University of Cape Town, Oxford University and the London School of Hygiene & Tropical Medicine have made a discovery that reveals how we can improve development of more effective vaccines against tuberculosis.

Biomarker study team
The SATVI team who worked on this research project. From left to right: Drs. Adam Penn-Nicholson, Sara Suliman, Professor Tom Scriba and Mzwandile Erasmus. 

The research team studied young children who had previously participated in a large clinical trail of a new tuberculosis vaccine conducted in Worcester. They investigated the immune response to BCG, given at birth, to determine characteristics of this response that are associate protective immunity against tuberculosis. “We looked at a number of factors that could be used as immune correlates, to try and find biomarkers that will help us develop a better vaccine.” said Professor Helen McShane from Oxford University, who led the study.

“We looked at a number of factors that could be used as immune correlates, to try and find biomarkers that will help us develop a better vaccine."

Professor Helen McShane, Oxford University

Tuberculosis is the biggest killer of humans due to bacterial infection. In 2014, 9.6 million people were diagnosed with Tuberculosis and 1.5 million died. The only available vaccine against tuberculosis, BCG, is given to infants to prevent severe forms of the disease but protection against lung disease is very variable, particularly in countries where TB is most common, such as South Africa.

Associate Professor Tom Scriba from the South African Tuberculosis Vaccine Initiative at the University of Cape Town said: “TB is still a major international killer, and rates of TB disease in some areas of South Africa are amongst the highest in the world. These findings provide important clues about the type of immunity TB vaccines should elicit, and bring us closer to our vision, a world without TB.”

"TB is still a major international killer, and rates of TB disease in some areas of South Africa are amongst the highest in the world."

Professor Tom Scriba, SATVI, UCT

 

The team carried out tests for twenty-two immune response characteristics and found that elevated activation of CD4 T cells was linked to higher TB disease risk. Higher levels of T cells, that responded to the BCG vaccine by producing the immune messenger molecule, IFN, were linked with reduced risk of TB.

Antibodies to the Ag85A protein made by the TB bacterium were also identified as a possible immune correlate. Higher levels of antibodies targeted against Ag85A were associated with lower TB risk. However, the team cautions that other environmental and disease factors could also cause Ag85A antibody levels to rise and so there may not be a direct link between these antibodies and TB risk.
Professor McShane said: ‘These are useful results which ideally would now be confirmed in further trials. They show that antigen-specific T cells are important in protection against TB, but that activated T cells increase the risk”.

Associate Professor Tom Scriba from the South African Tuberculosis Vaccine Initiative at the University of Cape Town said: “TB is still a major international killer, and rates of TB disease in some areas of South Africa are amongst the highest in the world. These findings provide important clues about the type of immunity TB vaccines should elicit, and bring us closer to our vision, a world without TB.”

Dr Helen Fletcher from the London School of Hygiene & Tropical Medicine, said: “For the first time we have some evidence of how BCG might work, and also what could block it from working. Although there is still much work to do, these findings may bring us a step closer to developing a more effective vaccine for TB."

Although there is still much work to do, these findings may bring us a step closer to developing a more effective vaccine for TB."

Dr Helen Fletcher, London School of Hygiene & Tropical Medicine.


The team is continuing its work to develop a new and improved TB vaccine, aiming to protect more people from the disease.

 

Citation: Zak DE, Penn-Nicholson A, Scriba TJ, Thompson E, Suliman S, Amon LM, Mahomed H, Erasmus M, Whatney W, Hussey GD, Abrahams D, Kafaar F, Hawkridge T, Verver S, Hughes EJ, Ota M, Sutherland J, Howe R, Dockrell HM, Boom WH, Thiel B, Ottenhoff THM, Mayanja-Kizza H, Crampin AC, Downing K, Hatherill M, Valvo J, Shankar S, Parida SK, Kaufmann SHE, Walzl G, Aderem A, Hanekom WA; ACS and GC6-74 cohort study groups. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet. 2016 Jun 4;387(10035):2312-2322. Click here.