RSV Vaccine with Nanoparticle-Based Poly-Sorbitol Transporter (PST) Adjuvant Improves Respiratory Protection Against RSV Through Inducing Both Systemic and Mucosal Humoral Immunity

<b>Background/Objectives:</b> Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T_RM) cells and tissue-resident memory B (B_RM) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses. However, the interactions between RSV vaccines and mucosal immune responses within the respiratory tract are poorly understood. We evaluated a mucosal immune system following immunization by RSV vaccine with poly-sorbitol transporter (RSV-PST), a nanoparticle adjuvant. <b>Methods:</b> We intranasally immunized the RSV-PST and identified the systemic and mucosal immune responses. Furthermore, we challenged with RSV A2 strain after immunization and investigated the protective effects. <b>Results:</b> Consequently, antigen-specific CD8⁺ T_RM cells were markedly elevated in the lung parenchyma, yet exhibited impaired cytokine expression. In contrast, humoral immunity, with systemic antibody production from serum, but not in the respiratory tract, was significantly increased by RSV-PST immunization. Interestingly, the production of respiratory mucosal antigen-specific IgG after RSV A2 challenge dramatically increased in the bronchoalveolar lavage fluid (BALF) of the RSV-PST immunized group in the presence of FTY720, and the lung-infected RSV titer was significantly lower in this group. Furthermore, after RSV A2 challenge, CD69⁺ IgG⁺ B_RM cells were significantly increased in lung tissues in the RSV-PST group. <b>Conclusions:</b> The RSV-PST vaccine has protective effects against RSV infection by promoting both systemic and local humoral immunity rather than cellular immunity.