Mucosal vaccines with STING-agonist liposomal formulations inhibit RSV (respiratory syncytial virus) replication in cotton rats

Respiratory syncytial virus (RSV) is responsible for severe lower respiratory tract infections (LRTI) in immunocompromised individuals. While recent breakthroughs in vaccine design have led to approved vaccines for the elderly, these vaccines are all administered through the parenteral route. Vaccine administration through the mucosal route could protect the viral route of entry and can be advantageous over injected vaccines. There is however a lack of safe and efficacious mucosal adjuvants that can facilitate both mucosal and systemic immune responses. Here, we present preclinical data based on liposomal nanoparticles, NanoSTING, that encapsulate the endogenous STING-agonist 2′3′-cGAMP (cyclic guanosine adenosine monophosphate) as adjuvant for prefusion protein-based intranasal vaccines against RSV. NanoSTING significantly increased the immunogenicity of well-documented RSV prefusion protein antigens DS-CaV1, sc9‐10 DS-CaV1, and SC-TM after a single intranasal dose, when compared to the protein-only and naked-cGAMP adjuvanted groups. Two doses of NanoSTING adjuvanted vaccines yielded robust secretory IgA titers at the mucosal surfaces and induced potent Th1 T-cell responses in the lungs of vaccinated mice. Both NanoSTING-sc9‐10 DS-CaV1 and NanoSTING-SCTM vaccines protect against viral replication at the upper (nose) and lower (lung) respiratory tract of RSV-challenged cotton rats. The ability of our mucosal vaccines against RSV to elicit immunity in the respiratory tract can prevent the establishment of infection in individuals and potentially prevent disease transmission.