Rosetrees researcher profile: Professor Helen Fletcher and Hannah Painter, London School of Hygiene and Tropical Medicine

Who Rosetrees Trust is funding

Tuberculosis (TB) is a leading cause of death from a single infectious agent. In 2018, 1.5 million deaths were reported and 10 million individuals developed TB active disease. This high mortality rate is largely due to the complexities of diagnosis and access to quality care for many. Multi- and extensively-drug-resistant TB remains a great global concern. The Bacille Calmette-Guérin (BCG) vaccine is currently the only clinically approved vaccine against TB. The vaccine provides some protection against severe forms of TB in children; however, protection against pulmonary TB in adults varies dramatically (between 0 and 80%). Despite recent breakthroughs in the TB vaccine pipeline, development and validation of TB vaccines remains slow, and understanding of the host immune response to Mycobacterium tuberculosis (Mtb), the causative agent of TB, remains poor. Extensive preclinical evaluation of candidate TB vaccines is a time-consuming and expensive process. To this end, TB vaccines are typically tested against laboratory strains of Mtb, despite reported variations in response to infection with different clinical isolates of Mtb in animal models.

Professor Helen Fletcher’s research at London School of Hygiene and Tropical Medicine focuses on TB vaccines and immune correlates of risk. In a recent review in Seminars in Immunology, Professor Fletcher highlights the growing interest in whole systems approaches to the identification of correlates of protection and progression to TB disease.

This project aims to accelerate the development of effective vaccines for protection against Mtb.

Hannah Painter said: “Tools which enable in-depth analysis of vaccine efficacy, as well as the underlying immune mechanisms associated with vaccination, are urgently required to improve and inform the TB vaccine pipeline.”

Professor Helen Fletcher and Hannah Painter

How Rosetrees Trust have supported Professor Helen Fletcher and Hannah Painter

Professor Helen Fletcher received Rosetrees Trust funding in 2016, to support Hannah Painter’s PhD which is due to complete later this year.

What the outcomes are of Rosetrees Trust-funded research from Professor Helen Fletcher and Hannah Painter

Professor Helen Fletcher and Hannah Painter have been successful in developing an ex vivo method to evaluate the efficacy of vaccines against diverse clinical isolates of Mtb in the mouse model. The use of the mycobacterial growth inhibition assay (MGIA) as a preclinical method to assess vaccine-induced protection was previously established in mouse spleen cells. The assay aims to provide a shorter and cheaper method of testing potential vaccine efficacy, generating data which may aid the design of traditional animal infection studies in a more cost-effective and informed manner.

The current work, published in Scientific Reports, has optimised the MGIA for use in both lung and spleen and streamlined the capacity of the assay for head-to-head testing of multiple Mtb strains or vaccines.

In addition, where variations in vaccine efficacy have been observed in the MGIA, flow cytometry and RNA-seq analysis have been performed to gain further insight into the mechanisms behind these observations.

Rosetrees Trust support on this project has helped the team secure further grants, including an MRC-BBSRC VALIDATE Pump Prime award, and an MRC National Productivity Fund placement award. Furthermore, this grant has supported PhD student, Hannah Painter, who has secured funding to continue to work on this project.

Written by: Dr. Rebecca Downing, Professor Helen Fletcher and Hannah Painter