Long-term effects of influenza and Bacille Calmette-Guérin vaccination on systemic inflammation

Chronic systemic inflammation can lead to metabolic, cardiovascular and neurodegenerative complications, but the factors influencing it are incompletely understood. In this study, we evaluated several factors, including Bacille Calmette-Guérin (BCG) and influenza vaccination, SARS-CoV-2 infection and sex, that may impact systemic inflammation as assessed by targeted inflammatory plasma proteome analysis in healthy individuals.

Participants were randomised to BCG or placebo vaccination at the start of the Dutch SARS-CoV-2 epidemic in March/April 2020. They reported their influenza vaccination status for the most recent influenza season. Twelve weeks after BCG or placebo vaccination, we assessed relative concentrations of 69 proteins in plasma of 357 individuals.

Both BCG and quadrivalent influenza vaccination were associated with overall trends towards reduced systemic inflammation in both sexes, but with a more pronounced effect in men. However, the impact on specific immunological proteins varied between BCG and influenza vaccinations. SARS-CoV-2 infection in the 12 weeks between randomisation and plasma sampling was also associated with overall trends towards reduced systemic inflammation, reaching significance for CXCL10 and TNF concentrations. Notably, individuals who had received BCG vaccination prior to SARS-CoV-2 infection did not exhibit this protein profile. Furthermore, elevated CXCL11 and OPG concentrations at 12 weeks were associated with subsequent respiratory symptoms during the additional 9 months of follow-up.

Our study revealed distinctive alterations in the plasma inflammation proteome associated with BCG vaccination, influenza vaccination, SARS-CoV-2 infection and sex. These findings are exploratory and hypothesis-generating and warrant further investigation in well-controlled longitudinal cohort studies.