Mucosal administration of anti-bacterial antibodies provide long-term cross-protection against Pseudomonas aeruginosa respiratory infection

International audienceBacterial 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

Mucosal administration of anti-bacterial antibody (Ab) provides long-term cross-protection against Pseudomonas aeruginosa respiratory infection

International audienceRespiratory infections are a major threat for global human health. The epidemic increase in antimicrobial resistance and seasonal virus outbreaks have severely complicated the management of respiratory infections. Airway administration of therapeutic antibodies demonstrated remarkable preclinical achievements against both viral and bacterial respiratory infections. The primary mode of action of antiinfective Ab is pathogen neutralization. However, using a mouse model of acute pneumonia induced by Pseudomonas aeruginosa lung infection, a versatile bacterium frequently associated with nosocomial infection and multidrug resistance, we also demonstrated immunomodulatory properties associated with anti-bacterial Ab. A single pulmonary administration of Ab efficiently contained the primary infection while being also able to trigger adaptive immunity providing a protecting long-term response against a secondary infection. This effect was specific and dependent on the dose of the antibody, the size of the inoculum and the presence of the cognate antigen. Thanks to adoptive transfer experiments, we showed that this long-term response was attributable to a sustained and protective humoral immunity. Remarkably, the long-lasting response mediated by a pulmonary-administered Ab allowed protection against secondary infections due to heterologous P. aeruginosa strains, expressing or not the cognate antigen. Overall, our findings suggest that mucosal delivery of Ab through the airways affords a rapid pathogen containment, while promoting long-term protection against secondary infections. This novel modality associated with anti-infective antibody opens new perspectives for the treatment of respiratory infections

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