BCG Vaccination Induces Trained Innate Immunity in Adults Over 50 Years of Age: A Randomized Trial in Guinea-Bissau

Abstract

Bacillus Calmette-Guérin (BCG) has beneficial effects on overall morbidity and mortality in children and young adults. These effects have been linked to a heterologous increase of pro-inflammatory cytokine production by innate immune cells. It is unknown if BCG induces similar responses in older individuals. In Guinea-Bissau, we randomized 40 adults over 50 years of age to BCG-Japan or placebo. Two months after vaccination, BCG-Japan recipients had higher production of IFN-γ to M. tuberculosis stimulation and increased release of the pro-inflammatory innate cytokines IL-1β, IL-6 and TNF-α to non-specific stimuli. These effects were more pronounced among those with a positive QuantiFERON at baseline.  Thus, BCG-Japan can induce a ‘trained immunity’ phenotype in older adults. These effects were boosted in previously Mycobacterium tuberculosis exposed individuals. Studies are warranted to assess whether BCG vaccination could be a tool to provide partial protection against infectious diseases in the elderly, including the new coronavirus SARS-CoV-2.

Keywords: Bacille Calmette-Guérin, trained immunity, non-specific effects of vaccines, heterologous effects, immunosenescence, COVID-19.