TB trial highlights the challenges of introducing new childhood vaccine

Child being vaccinated, The Gambia

The findings may have important implications for designing the most effective immunisation schedules for children and for the design of future clinical trials of the new vaccine.

Standard childhood vaccinations are routinely given as part of a schedule known as the Expanded Program on Immunisation, or EPI, which helps to improve vaccine coverage in the population by reducing the number of visits to the clinic required. The schedule includes vaccines for diphtheria, tetanus and whooping cough, as well as the current vaccine for tuberculosis, Bacille Calmette-Guérin (BCG). The aim is to vaccinate children in early infancy to protect them from disease as early as possible.

With 1.8 million people per year killed by tuberculosis and more than 2 billion people worldwide infected with the bacteria that cause the disease, it is clear that BCG offers limited protection and that there is an urgent need for more effective vaccines against tuberculosis.

MVA85A is a vaccine designed to be given after BCG to boost the body’s immune response and improve protection against tuberculosis. Originally developed by Dr Helen McShane at the University of Oxford with funding from the Wellcome Trust and the Medical Research Council (MRC), it has already been shown to be safe and capable of eliciting powerful immune responses in clinical trials in adults in the UK, The Gambia and South Africa.

This is the first trial to evaluate the safety of the vaccine in infants. The purpose of the study was to assess whether MVA85A can stimulate immune responses against the tuberculosis bacteria in infants and whether it could feasibly be given at the same time as other childhood vaccines as part of the EPI.

The randomised trial, funded by the Wellcome Trust, the MRC and the European Commission, involved 214 healthy four-month-old infants, who had already received BCG at birth. Children were given the EPI alone, MVA85A alone or MVA85A in conjunction with the EPI.

Overall, MVA85A was deemed to be safe and well tolerated and induced a strong immune response. Importantly, the responses to the standard EPI vaccines were not affected by giving MVA85A at the same time; however, the immune response to MVA85A was lower in infants who received it in conjunction with EPI vaccines than in infants that received the new vaccine alone.

Dr McShane, a Wellcome Trust Senior Clinical Research Fellow at the University of Oxford, explains: “It’s reassuring to see that MVA85A does not affect immunity to the other vaccines that are included in the EPI and important to see that it is safe in infants. This study will help us determine the best way to integrate MVA85A into routine infant immunisation schedules in future.”

Dr Martin Ota, who led the study at the Medical Research Council (MRC) Unit in The Gambia, welcomes the results: “These important results highlight that we have a real opportunity to make sure that children are protected in the future against tuberculosis by introducing effective and well-timed immunisation programmes. This can only be achieved with robust information gathered from well-conducted clinical trials such as this.”

“We don’t yet know how the immune response we generate with MVA85A relates to protection from TB and we are currently conducting an efficacy trial of a higher dose of the vaccine in South African BCG-vaccinated infants to assess this. The results of this trial will be available in 2012,” added Dr McShane.

The South African efficacy trial of MVA85A is supported by a Wellcome Trust Strategic Translation Award. Supporting research to combat infectious disease is one of the Wellcome Trust’s strategic goals.

Dr Ted Bianco, Director of Technology Transfer at the Wellcome Trust, commented: “The EPI has been enormously important in protecting successive generations of children from preventable infections for over 20 years. But a limitation of the programme is that not all vaccines can be easily accommodated within a universal vaccination schedule. It is one of the great challenges in public health to resolve this conundrum so that the fruits of today’s vaccine research can be delivered to where they are needed with the efficiency that underpins the success of the EPI.”

Image: A child being vaccinated. Credit: MRC Unit, The Gambia.


Jen Middleton
Media Officer, Wellcome Trust
020 7611 7262
07534 143849
[email protected]


M. Ota et al. Immunogenicity of the tuberculosis vaccine MVA85A is reduced by coadministration with EPI vaccines in a randomised controlled trial in Gambian infants. Sci Trans Med 2011 [epub ahead of print]


The study was funded by the Medical Research Council (UK) and the European Commission (EU 6th Framework; TBVAC). Dr Helen McShane is a Wellcome Trust Senior Clinical Research Fellow and Professor Adrian Hill is a Wellcome Trust Principal Research Fellow.

Notes to editors

About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.

About the University of Oxford
Oxford University’s Medical Sciences Division is recognised internationally for its outstanding research and teaching, attracting the brightest minds from all over the world.

It is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students, and brings in around two-thirds of Oxford University’s external research income. Listed by itself, that would make it the fifth largest university in the UK in terms of research grants and contracts.

Oxford is home to the UK’s top-ranked medical school, and partnerships with the local NHS Trusts enable patients to benefit from the close links between medical research and healthcare delivery.

14 winners of the Nobel Prize for Physiology or Medicine worked or were educated at Oxford, and the division is home to 29 Fellows of the Royal Society and 68 Fellows of the Academy of Medical Sciences.

Past successes include the development of penicillin, which ushered in the modern age of antibiotics, and the confirmation of the link between smoking and cancer, which has prevented many millions of deaths. Oxford continues to be at the forefront of medical research, whether it’s the genetic and molecular basis of disease, the latest advances in neuroscience, or clinical studies in cancer, diabetes, heart disease and stroke. Oxford has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic.

A major strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies into the causes and treatment of cancer, heart disease, diabetes and other common conditions.

About the Medical Research Council
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century.