Layer-by-Layer Microparticle Vaccines Containing a S177Q Point Mutation in the Central Conserved Domain of the RSV G Protein Improves Immunogenicity.

Respiratory syncytial virus (RSV) is a significant cause of disease in the young and old. Recently, pre-fusion F protein vaccines for RSV have received food and drug administration (FDA) approval to protect adults aged 60 years and older; however, vaccines evaluated against RSV typically do not elicit complete or durable protective immunity. We previously showed that an RSV G protein central conserved domain (CCD) nanoparticle vaccine containing an S177Q mutation (NP-S177Q) induced favorable immunogenicity and RSV-neutralizing antibodies compared with RSV G protein vaccination alone in mice. Boosting BALB/c mice with NP-S177Q vaccines improved correlates of protection and reduced markers of immunopathology following RSV challenge. This study examined microparticle (MP) vaccines displaying the CCD with an RSV G S177Q mutation (MP-S177Q) adjuvanted with monophosphoryl lipid A (MPLA) in BALB/c mice. Our findings show that mice adjuvanted MP-S177Q vaccination develop effective viral neutralization compared with MP-WT and MP-S177Q vaccination and have improved bronchoalveolar Th1-type cytokine responses following the RSV challenge compared with MP-WT or vehicle-vaccinated mice. This study shows that a rationally mutated RSV G protein MP vaccine is safe, effective, and can advance precision RSV vaccines.