Oxford University Clinical Academic Graduate School

Women in Science interview

Chasing the TB Vaccine (PDF)

Since 2001, the McShane Group has worked to design and develop novel tuberculosis (TB) vaccine candidates, testing them first in preclinical animal models, and then in clinical trials – first in the UK and then in high burden countries including South Africa, Uganda, Senegal and The Gambia.

TB kills more people than any other infectious disease. The HIV epidemic and the emergence of multi and extensively drug-resistant strains of Mycobacterium tuberculosis (M.tb) mean that global control of tuberculosis (TB), particularly adult pulmonary TB, remains inadequate. There is an urgent need for better control measures, and the most cost-effective way to control any infectious disease epidemic is with effective vaccination. The current vaccine, BCG confers protection against disseminated disease in childhood, but does not reliably protect against pulmonary disease. Vaccine development is challenging given the lack of defined immune correlates of protection and uncertain predictive value of preclinical animal models.

The McShane Group led the development of MVA85A (recombinant modified vaccinia Ankara expressing antigen 85A), the first new TB vaccine to enter clinical trials in 2002 and the first to be tested in an infant efficacy trial in 2009. MVA85A was safe and immunogenic but did not improve BCG induced protection in BCG-vaccinated South African infants (Tameris et al, Lancet 2013).

Since 2013, the group has focused on 4 main areas:

1. Identification of novel candidate antigens and optimisation of antigen delivery systems in preclinical animal models (Stylianou et al, Front Immunol 2023; Korompis et al, Sci Reports 2025).
2. Evaluation of mucosal delivery of candidate TB vaccines including BCG, MVA85A and ChAdOx1 85A (Satti et al, Lancet Infect Dis 2014; Audran et al, Journal of Infection 2024).
3. Establishment and validation of two TB (BCG) human challenge models using skin and aerosol challenge (Harris et al, JID 2014; Satti et al, Lancet Infect Dis 2024).
4. Identification of immune correlates of risk from samples taken in the infant efficacy trial (Fletcher et al, Nature Comms 2016; Satti et al, Nature Comms 2022).

Since 2021, the group has also been establishing a controlled human infection for SARS CoV-2, establishing a platform for human infection studies to accelerate next-generation COVID-19 vaccines and therapeutics and to inform preparedness for future pandemics. (Jackson et al, Lancet Microbe 2024). We are currently evaluating an Omicron BA.5 subvariant of SARS-CoV-2.

IMPAc-TB

The Immune Mechanisms of Protection Against Mycobacterium tuberculosis Centers (IMPAc-TB) program is an initiative established by NIAID in 2019 to elucidate the immune responses needed to protect against infection with Mycobacterium tuberculosis (M.tb). The program will lead to a better understanding of tuberculosis (TB) immunology, which is critical to guide the design and development of new and improved TB vaccines, and it aligns with the goals of the NIAID Strategic Plan for Tuberculosis Research.

Visit IMPAc-TB Site