Towards a better TB vaccine: understanding improved local immune control by mucosal BCG vaccination

Towards a better TB vaccine: understanding improved local immune control by mucosal BCG vaccination

Led by Dr Paula Niewold (LUMC, The Netherlands), with Dr Frank Verreck (BPRC, The Netherlands)

 

Tuberculosis is an infectious disease of the lung caused by Mycobacterium tuberculosis. It can spread between people via coughing and yearly 10 million people become infected, with 1.5 million people dying as a result of infection. Treatment consists of multiple months of antibiotics, but infection is becoming more difficult to treat as antibiotic resistance is increasing. Furthermore, the only approved vaccine, BCG, has limited efficacy. Ongoing attempts to develop improved vaccines are hampered by a lack of knowledge on the characteristics of the optimally effective immune response against Mycobacterium tuberculosis.

 

Non-human primates are an important representative model for human infection with Mycobacterium tuberculosis as they have an immune system and disease presentation very similar to humans. Recent studies in this animal model have shown that BCG vaccination in the lung, e.g. the site of Mycobacterium infection, results in a more effective protection than standard BCG vaccination in the skin. Here, we want to find out why and how lung vvaccination improves protection against infection. To achieve this, we will compare lung material from animals that were BCG vaccinated in the skin or lung and subsequently infected with Mycobacterium tuberculosis. We will study the organisation of immune cells within the lung as well as the type of cells present at the site of infection to explain why lung vaccination gives a more protective response against Mycobacterium tuberculosis than skin vaccination.

 

This knowledge will help us understand which immune responses are required to control Mycobacterium tuberculosis infection and disease. This will inform improved vaccine design to achieve better protection against Mycobacterium tuberculosis infection and ultimately reduce the burden of tuberculosis.

Paula Niewold
Frank Verreck