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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.

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 are currently conducting a clinical trial in HIV infected subjects, and to date this vaccine is also safe and highly immunogenic in this group.

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.  We are currently conducting a non-interference study in Gambian infants to see if co-administration of MVA85A and the routine EPI vaccinations results 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.

In 2008, we plan to begin a proof-of-concept Phase IIb efficacy trial of boosting BCG with MVA85A in infants in Worcester. The results of this study should be available in 2011.

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.

Slides from Dr Helen McShane's Jenner Seminar

Standard Operating Procedures for MVA85A trials

MVA85A Potency Assay

MVA85A Identity and Purity PCRs

SOP for Sequencing Vaccine Antigens

Ex Vivo ELISPOT

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