Intranasal delivery of a polymeric nanoparticle subunit vaccine for the induction of protective immunity against respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children under the age of 5, worldwide. Maternal vaccination and monoclonal antibodies provide only temporary protection for young children. As antibody wanes, young children remain at risk for severe RSV disease, creating an unmet need for a direct childhood vaccine. We developed an intranasal (IN) subunit vaccine, comprised of a biotinylated nanoparticle and RSV prefusion protein DS-Cav1 (PreF-bNP) with a flexible "plug-n-play" design that enables dose optimization of antigen and adjuvants. In a preimmune RSV mouse model, immunization with intranasal PreF-bNP increased IL-12+ dendritic cells, generated Th1- polarized CD4 effector and tissue resident memory T cells (TRMs) and established antiviral CD8 TRMs in the lung. PreF-bNP-mediated antiviral responses correlated with complete RSV protection up to 8 weeks with reduced mucus production in the lungs. Together, the data presented demonstrate that intranasal PreF-bNP safely protects against RSV infection in young preimmune mice and should be further investigated for future clinical development.