Bacterial respiratory infections either acute or chronic are major threats for human health. Direct mucosal administration, through the airways, of therapeutic antibodies (Ab) offers a tremendous opportunity to benefit to patients with respiratory infections. The mode of action of anti-infective antibodies relies on pathogen neutralization and Fc-mediated recruitment of immune effectors to facilitate their elimination. Using a mouse model of acute pneumonia induced by P. aeruginosa, we depicted the immunomodulatory mode of action of a neutralizing anti-bacterial Ab. Beyond the rapid and efficient containment of the primary infection, the Ab delivered through the airways harnessed genuine innate and adaptive immune responses to provide long-term protection, preventing from a secondary bacterial infection. In vitro antigen-presenting cells stimulation assay, as well as in vivo bacterial challenges and serum transfer experiments indicate an essential contribution of immunes complexes with the Ab and pathogen in the induction of the sustained and protective antibacterial humoral response. Interestingly, the long-lasting response protected partially against secondary infections with heterologous P. aeruginosa strains. Overall, our findings suggest that Ab, delivered mucosally, promotes bacteria neutralization and provides protection against secondary infection. This opens novel perspectives for the development of anti-infective Ab delivered to the lung mucosa, to treat respiratory infections.