Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection and is responsible for substantial morbidity and >100,000 worldwide deaths annually. RSV was described in the 1950s, yet to date there remains no safe and effective RSV vaccine, and therapeutic interventions are limited. The main consideration in RSV vaccine development is balancing safety and immunogenicity. A major tragedy occurred when a formalin-inactivated RSV (FI-RSV) vaccine trial in infants caused enhanced respiratory disease (ERD) and two deaths following RSV infection. RSV causes repeat infections throughout life, particularly in the immune compromised, those with inadequate cardiac or pulmonary systems, and the elderly who are at risk for severe complications. The at-risk populations and poor natural immunity to RSV infection are challenges with inducing a protective immune response. RSV vaccine development has primarily concentrated on the two major surface proteins, i.e., the fusion (F) and the attachment (G) proteins. The F protein is a primary target for vaccine development because of its conservation between RSV subtypes. Also, Palivizumab, a prophylactic, humanized monoclonal antibody (mAb) targets the F protein. The G protein is less conserved than the F protein, however the G protein has a central conserved domain (CCD) (164-176) and highly conservedCX3C chemokine motif (182CWAIAC187). The CX3C motif attaches to ciliated respiratory epithelial cells , and soluble and/or membrane-bound RSV G protein competes with endogenous fractalkine for CX3CR1 binding, disrupts T cell trafficking in the lung, and modulates the host anti-viral responses. Thus, the G protein and its CX3C motif are integral to RSV infection and modulating the host immune response. Central to the rationale of this dissertation, anti-G protein antibodies (Abs) may block G protein CX3C-CX3CR1 interaction, inhibit RSV replication, reduce inflammation, and reduce disease pathogenesis. Thus, the RSV G protein is important in both mediating immunopathology and inducing protective immune responses. Herein, we describe improved immunogenicity of G protein mutant vaccine candidates, further development of top-line candidate (S177Q) in a nanoparticle vaccine platform, and effective prophylactic and therapeutic anti-G mAbs.