Charlotte Thålin: Respiratory IgA and Protection against Infection: Insights from Longitudinal Surveillance in a Swedish Healthcare Worker Cohort

Respiratory IgA and Protection against Infection: Insights from Longitudinal Surveillance in a Swedish Healthcare Worker Cohort

Respiratory viruses such as corona-, influenza- and respiratory syncytial viruses initiate infection at mucosal surfaces of the respiratory tract. Yet, current vaccines primarily elicit systemic immunity, with limited induction of mucosal antibodies and a limited protection against respiratory infections.

Through longitudinal surveillance of serum and respiratory antibodies in the Swedish COMMUNITY healthcare worker cohort, we have shown that pre-existing respiratory IgA is associated with a reduced risk of subsequent infection, highlighting its protective role and the importance of including mucosal endpoints in vaccine evaluation.  Respiratory infections consistently induce virus-specific mucosal IgA in the upper airways and repeated mucosal exposures elicit enhanced and long-lasting mucosal IgA responses, strengthening the rationale for developing effective mucosal vaccines.  Furthermore, while systemic vaccination remains essential for preventing severe disease, our findings suggest that repeated vaccinations may influence subsequent generation of mucosal IgA trough a reduction of viral load and inflammation in the mucosa, which is highly relevant for both understanding the development of population immunity and for optimizing the timing of a sequential systemic and mucosal vaccination approach. Building on these findings, we are now exploring the structural and functional properties of secretory IgA in the respiratory mucosa using liquid chromatography–mass spectrometry and human nasal and lung organoid models. These complementary approaches aim to unravel how IgA protects us at the respiratory mucosa, ultimately guiding the development of IgA-based interventions for enhanced protection against respiratory infections.