Intranasal administration of vaccines is an attractive delivery route to fight viral respiratory infections. However, there are only a few intranasal vaccines used in human, emphasizing the critical need to identify novel safe mucosal adjuvants and antigen delivery systems to expand their usage. We recently revealed an immunostimulating nanoparticle based on a fragment (R4R5) of the Curli-specific gene A (CsgA) protein that confers protection against influenza A virus (IAV) when conjugated to three repeats of the highly conserved M2e epitope and administrated intramuscularly. Herein, the efficacy of this 3M2e-R4R5 nanovaccine was investigated upon administration by intranasal instillation. By triggering robust M2e-specific humoral and cellular responses, both systemic and locally in the respiratory tract, and by priming alveolar macrophages, the intranasal vaccine protected mice against a lethal IAV challenge without the use of additional adjuvant. Thus, CsgA-based nanostructures could serve as a safe and self-adjuvanted antigen delivery system for mucosal immunization.