Does BCG protect infants from severe forms of childhood tuberculosis by trained innate and humoral mechanisms?

Department of Immunology and Infection

PhD Upgrading Seminar

Tuesday 11th September

12:30 Lucas Room (LG81)

Does BCG protect infants from severe forms of childhood tuberculosis by trained innate and humoral mechanisms?

Speaker: Egle Butkeviciute

Supervisors: Steven Smith and Christine Jones (SGUL)

 

 A L L  W E L C O M E

 

 

According to the WHO, in 2016, TB was the tenth leading cause of death. In 2015, around 191,000 TB deaths occurred in children <5 years of age. Increased risk of pulmonary TB and its complications in infants is thought to occur due to diminished inflammatory responses.

Mycobacterium bovis BCG, the currently used anti-TB vaccine, prevents thousands of disseminated or meningeal TB cases in children. BCG is thought to induce Th1-type responses and activate monocytes or alveolar macrophages via enhanced IFNγ or TNFα production, improving their mycobactericidal properties. Despite these responses being detectable in vaccinated infants, some develop active disease, with others remaining protected, implicating that other mechanisms may be involved in protection from TB.

Trained innate immunity – the ability of the innate immune cells primed with an immunological challenge to respond to secondary stimuli more rapidly and to a higher extent – might contribute to BCG effectiveness against TB. Monocytes trained with BCG in vitro or isolated from BCG-vaccinated individuals express higher levels of activation markers and inflammatory cytokines upon challenge with Mycobacterium tuberculosis, suggesting that BCG vaccination might polarise infant immune responses towards a more inflammatory phenotype through induced training of monocytes.

In addition, BCG-induced mycobacterial antibodies may play a role in infant protection from TB. IgG against mycobacterial antigen Ag85A has been recently associated with infant protection from M. tuberculosis infection. In BCG-vaccinated adults, anti-arabinomannan- and anti-lipoarabinomannan- specific antibodies containing sera may improve phagocyte mycobacterial capture, phagocytosis and killing, suggesting that humoral immunity could contribute towards infant protection against TB.

This project will investigate whether infant BCG immunisation induces a trained phenotype in monocytes of the vaccinated infants and whether this phenotype is protective against M. tuberculosis. It will also test whether BCG-induced antibodies improve phagocyte responses to M. tuberculosis infection.

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