Human Tuberculosis Vaccine Programme

Programme Leader: Prof Helen McShane

Clinical Trial Programme

Heterologous prime-boost vaccination regimens provide an effective way to induce high levels of cellular immunity. Since 2002, we have been developing a new vaccination strategy for human tuberculosis using BCG as a priming vaccination and boosting with a recombinant modified vaccinia Ankara expressing antigen 85A (MVA85A). The inclusion of BCG in a new regimen allows the retention of the protective effects of BCG in childhood against severe disease.

Phase I clinical trials in the UK

In 2002, we began a series of small scale clinical trials with MVA85A to investigate the safety and immunogenicity of this vaccine when used alone, when used as a booster vaccine for BCG primed subjects, and when used as a post –exposure vaccine in subjects latently infected with M.tuberculosis. We have found that MVA85A is extremely safe and highly immunogenic when administered to BCG naïve subjects, and is significantly more immunogenic when administered to subjects previously primed with BCG (McShane H et al, Nature Medicine 2004). MVA85A is also safe and highly immunogenic when administered to M.tb latently infected subjects. We have also conducted clinical trials in HIV infected subjects, and the vaccine is safe and highly immunogenic in this group.

Phase II clinical trials in Africa

As a result of the success of the UK clinical trials described above, we conducted in 2003 two clinical trials in adults in The Gambia, as a collaboration with the MRC Laboratories, Fajara, including a non-interference study in Gambian infants to see if co-administration of MVA85A and the routine EPI vaccinations resulted in any interference between the vaccines.

Since 2005, we have also been conducting a series of Phase IIa clinical trials in the Western Cape in South Africa as a collaboration with Professor Greg Hussey at the University of Cape Town (South African Tuberculosis Initiative). We have vaccinated adults and adolescents at Worcester, and again see an excellent safety profile and high levels of vaccine induced immunogenicity.

Current efficacy trials

MVA85A is currently in two large scale phase IIb efficacy trials in Africa. The first, which started in 2009, supported by Aeras and Wellcome Trust, has fully enrolled 2797 South African infants who were randomised to receive BCG alone at birth or BCG followed by MVA85A at five 4-6 months of age. Results from this trial will be available in summer 2012. A second phase IIb efficacy trial started in summer 2011 in HIV-infected adults in South Africa and Senegal, largely supported by EDCTP funding. Cellular immunology programme

Our main immunological readout in all of the clinical trials outlined above is the ex-vivo interferon gamma Elispot assay. However we have cryopreserved PBMC from all subjects at all time points in all of these clinical trials and are conducting a comprehensive analysis of the function and phenotype of these cells.

Preclinical programme

There are several preclinical models of human tuberculosis and we have an active programme of research, both in house and through collaborations with other institutions, in working on evaluating new vaccines in these models.

Group members

Helen McShane, Programme Leader
Helen Fletcher, Postdoc
Kristin Griffiths, DPhil student
Stephanie Harris, Research Assistant
Rachel Kandt, DPhil student
Magali Kostov, DPhil student
Alison Lawrie, Senior Vaccine Development Co-ordinator & Clinical Project Manager
Dr Zita-Rose Manjaly, Academic Clinical Fellow and Specialist Trainee
Murielle Millard, PA to Helen McShane and Clinical Trials Secretary
Dr Jenny Piercy, Jenner Fellow
Ian Poulton, Study Coordinator
Hazel Poyntz, DPhil student
Iman Satti, Postdoc
Elena Stylianou, Post-grad RA
Rachel Tanner, Research Assistant
Samantha Vermaak, TB Vacccine Programme Coordinator