Effect of the BCG vaccine on the immune system and general health in the elderly, including the response to seasonal influenza vaccination.

The aim of this project is to explore the effect of BCG vaccination on the immune system and general health of senior citizens.
The BCG (Bacille Calmette Guerin) vaccine was developed for tuberculosis prevention, but there is increasing evidence that it also has beneficial heterologous ‘non-specific’ effects on the immune system. Studies among children in low-income countries have shown that BCG vaccination reduces neonatal mortality far more than can be explained by prevention of tuberculosis. BCG strengthens the innate immune system resulting in increased activity against non-related infections in laboratory models, a term named “trained immunity”. Recent studies suggest there might be an effect in older adults as well as in children.
With increasing age, we experience a general decline in immune function resulting in increased susceptibility towards infections and a lower vaccine efficacy. It is therefore relevant to explore potential means to improve immune function in the elderly. The project consists of two randomized controlled trials including a total of 2000 participants over 65 years of age.
In Study 1 (BCG-DENMARK-SENIOR, EudraCT number 2020-003904-15) participants are randomized 1:1 to BCG vaccination or placebo and followed for 12 months. The objectives are to reduce the risk of acute infections in general and COVID-19 in particular.
In Study 2 (BCG-DENMARK-INFLUENZA, EudraCT number 2019-002781-12) participants are randomized in to four groups exploring the effect of different combinations of influenza vaccination and BCG vaccination with the aim to improve the immunological response to influenza vaccination and study the effect on the immune system and induction of trained immunity.
BCG is a low risk, low cost, easily manageable intervention. If effective as a booster of immune function in the elderly, it could help reduce the pressure on our health system and potentially mitigate the effect of future pandemics.