In the present study, the investigators want to investigate whether prior BCG-vaccination improves the efficacy of influenza ("the flu") vaccination in young and/or old healthy volunteers and consequently could protect against influenza virus infection.

Influenza virus infection leads to millions of cases of severe illnesses worldwide and up to an estimated 500.000 deaths annually. The potential for the sudden emergence of pandemic influenza strains represents an incessant threat on even a larger scale. seasonal influenza vaccination is the backbone of influenza management. However, antibodies generated by vaccination, most often do not effectively neutralize emergent strains due to the high mutation rate of the influenza viral genome. In addition, although vaccination is effective in up to 85% of healthy adults, only 40-60% of the elderly are able to mount an protective antibody response due to an agerelated decline in immune function (so-called immunoscenescence). As a result, the protective effects of influenza vaccination are limited, and strategies to improve host immune defenses against influenza virus infection per se, and following influenza vaccination, are highly warranted.

It is suggested that prior vaccination with Bacille Calmette-Guérin (BCG) could enhance resistance to other infectious diseases in addition to protection to tuberculosis (TBC) and, in mice, protection of prior BCGvaccination against influenza infection was demonstrated long ago. However, only recently substantial evidence for these nonspecific beneficial effects of BCG-vaccination in humans has been provided by several randomized clinical trials. Considering these potentiating effects of BCG-vaccination, it could be a viable strategy to improve efficacy of influenza vaccination, and/or enhance immune defenses against influenza virus infection per se. If so, this would have an enormous impact on clinical practice.

Inclusion Criteria:

• Age ≥18 and ≤35 yrs
• Male
• Healthy

Exclusion Criteria:

• History of influenza vaccination within the year prior to study entry
• History of BCG vaccination within 5 years prior to study entry
• History of Mantoux testing within the year prior to study entry
• Vaccination other than BCG or influenza, within 3 months prior to study or within study period
• Medical history of any disease associated with immune deficiency
• Clinically significant acute illness, including infections, within 4 weeks before vaccination
• Participation in a drug trial or donation of blood 3 months prior to study entry
• Use of recreational drugs within 21 days prior to experiment day
• Recent hospital admission or surgery with general anaesthesia (<3 months)
• Known chronic kidney or liver disease
• Latent or active tuberculosis infection