Summary Clinically, AOM is the leading reason for pediatrician visits and antibiotic usage by children. The predominant causative agents of AOM are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. While currently licensed capsule-based vaccines have dramatically lowered in the incidence of invasive pneumococcal disease, the incidence of mucosal infections such as AOM has remained relatively unchanged. Likewise, non-typeable H. influenzae currently predominates the AOM landscape following introduction of the Hib vaccine. Additionally complicating matters is the potential concern that a vaccine targeting an individual otopathogen may not reduce overall incidence of AOM due to the non-targeted pathogens becoming more predominant following the removal of an individual pathogen. We have engineered a safe, effective, and highly manipulatable platform for delivering protein epitopes to the mucosal surface to target multiple otopathogens simultaneously while engendering protective immunity at the mucosal surface. Leveraging a combinatorial approach for eliminating multiple AOM pathogen simultaneously using a live vaccine platform to maximize mucosal antibody responses represents a novel strategy for reducing the burden of AOM in children.