Copyright © 2015 by The American Association of Immunologists, Inc. Invasive aspergillosis (IA) resulting from infection by Aspergillus fumigatus is a leading cause of death in immunosuppressed populations. There are limited therapeutic options for this disease and currently no vaccine. There is evidence that some anti-A. fumigatus mAbs can provide protection against IA. However, vaccine development has been impeded by a paucity of immunological targets on this organism demonstrated to provide protective responses. Sialylated oligosaccharide epitopes found on a variety of pathogens, including fungi and group B streptococci (GBS), are thought to be major virulence factors of these organisms facilitating pathogen attachment to host cells and modulating complement activation and phagocytosis. Because some of these oligosaccharide structures are conserved across kingdoms, we screened a panel of mAbs raised against GBS serotypes for reactivity to A. fumigatus. This approach revealed that SMB19, a GBSIb type-specific mAb, reacts with A. fumigatus conidia and hyphae. The presence of this Ab in mice, as a result of passive or active immunization, or by enforced expression of the SMB19 H chain as a transgene, results in significant protection in both i.v. and airway-induced models of IA. This study demonstrates that some Abs generated against bacterial polysaccharides engage fungal pathogens and promote their clearance in vivo and thus provide rationale of alternative strategies for the development of vaccines or therapeutic mAbs against these organisms.