Yona Tugg, McMaster University

Yona Tugg (1), Karena Wong (1), Kyle Amaral (1), Sam Afkhami (1), Matthew S. Miller (1). 1. McMaster University

Fighting & Responding

Infection caused by influenza A virus (IAV) leads to significant morbidity and mortality every year. Protection provided from vaccines varies from season to season. Recent research has turned to broadly-neutralizing antibodies (bNAbs) that bind to the stalk domain of hemagglutinin, which is more conserved across strains than the head domain. Broadly-neutralizing antibodies protect against a broader range of viral strains and function by recruiting and activating immune effector cells. Most research focuses on IgG bNAbs of, as they are most dominant in human serum. However, IgA antibodies, which are most dominant at mucosal surfaces, have been relatively understudied. Broadly-neutralizing IgG antibodies require Fc-FcγR interactions for protection against IAV in vivo. Little is known about the role of IgA and Fc-Fc⍺RI interactions in the context of IAV infection, mainly due to a lack of an appropriate animal model. Mice do not have a native Fc⍺RI. To address this, we used a transgenic mouse model expressing human FcαRI to investigate the Fc-mediated functions of IgA bNAbs during IAV infection. Broadly-neutralizing IgA was passively transferred to wild-type and transgenic mice following IAV challenge. Transgenic mice receiving mucosally-delivered IgA were protected from morbidity and mortality and had reduced viral burden compared to wild-type controls. Histological analysis revealed more extensive inflammation and epithelial damage in the lungs of wild-type mice. These findings underscore the significance of FcαRI in mediating IgA-dependent immunity and offer valuable insights for the development of next-generation vaccines and therapies.