Stephanie Harris Poster 2023

Stephanie Harris

Mrs Stephanie Harris

Jenner Institute, UK

Developing a Controlled Human Infection Model with Intradermal or Aerosol BCG as a Surrogate for M. tb Infection

 

 

Poster Abstract

We do not currently have a correlate of protection against Mycobacterium tuberculosis (M. tb) or the ability to safely challenge humans with virulent M. tb in order to evaluate candidate vaccines. Using an in-vivo bacille Calmette-Guérin (BCG) controlled human infection model (CHIM) as a surrogate for M. tb infection, it is possible to assess in-vivo anti-mycobacterial immunity and to identify laboratory markers of the immune response that correlate with levels of mycobacterial suppression.

Using an intradermal BCG infection model and quantifying BCG from a skin biopsy taken at the injection site 14 days later, we have shown a significant vaccine effect in volunteers who have previously been BCG-vaccinated compared to those who were BCG-naïve.

As the natural route of M.tb infection is via inhalation of aerosolised droplets and not through the skin, we have also been developing an aerosol BCG infection model. In BCG-naïve volunteers, we have shown that BCG is recoverable from bronchoalveolar lavage fluid at 2, 7 and 14 days post-infection. We are now investigating the safety and BCG recovery in volunteers who have previously had BCG vaccination.

Both the intradermal and aerosol BCG CHIMs could be a valuable tool in identifying correlates of protection and in the down-selection of candidate vaccines to progress to expensive efficacy trials.

 

Biography

I am a Senior Research Assistant in Helen McShane's Tuberculosis research group at the Jenner Institute. My main role is managing the laboratory side of the tuberculosis clinical trials; preparing for new trials, processing samples from trial volunteers and carrying out immunological assays to assess the response to candidate vaccines. Current trials are investigating the immune response to aerosol BCG and we are developing controlled human infection models (CHIMs) using intradermal and aerosol BCG as surrogates for M. tb infection. Since 2021, we have also been working on establishing a CHIM for SARS-CoV-2, to help understand the immune response needed for protection in the ongoing fight against COVID-19.