α-1,3-Glucan-Driven Remodeling of the Conidial Cell Wall in an <i>Aspergillus fumigatus</i> Vaccine Strain Alters Innate Immune Recognition

<i>Aspergillus fumigatus</i> is a major cause of invasive aspergillosis in immunocompromised patients, where current antifungal therapies are limited by toxicity, drug resistance, and lack of durable protection, and no vaccines are available. A mutant lacking the sterylglucosidase-encoding gene (<i>sglA</i>) has emerged as a candidate that induces protective immune responses, but the structural basis for this phenotype remains unclear. Here, we use cellular solid-state NMR spectroscopy to compare the organization of the conidial cell wall in Δ<i>sglA</i> and its wild-type counterpart. The Δ<i>sglA</i> conidial cell wall displays extensive remodeling, including increased α-1,3-glucan content and structural polymorphism, strengthened interactions with β-glucans, reduced hydration, and restricted molecular motion, together consolidating a more rigid scaffold with limited β-glucan accessibility. These structural changes are associated with altered neutrophil responses and a shift in innate immune signaling. This work links cell-wall reorganization to altered immune recognition in this vaccine candidate, with implications for future immunotherapeutic strategies.