Mannose derivative and lipid A dually decorated cationic liposomes as an effective cold chain free oral mucosal vaccine adjuvant-delivery system

•Mannose-PEG-cholesterol (MPC) was synthesized to prepare MPC/lipid A-liposomes (MLL).•Ag-loaded proMLL were prepared by emulsification-lyophilization and stable at 25 °C.•Ag-MLL formed from proMLL were a cold-chain-free vaccine adjuvant-delivery system.•Ag-MLL given to mice via oral mucosa induced robust systemic/mucosal immunoresponses.•Ag-MLL given to mice via oral mucosa induced a blended Th1/Th2 type immune response.

To develop convenient, effective cold chain-free subunit vaccines, a mannose-PEG-cholesterol conjugate (MPC) was synthesized as a lectin binding molecule and anchored onto liposomes which entrapped lipid A and model antigen to form a vaccine adjuvant-delivery system targeting antigen presenting cells. With MPC, soy phosphatidylcholine, stearylamine and monophosphoryl lipid A as emulsifiers dissolved in oil phase (O), and sucrose and BSA in water phase (W), the O/W emulsions were prepared and subsequently lyophilized. The lyophilized product was stable enough to be stored at room temperature and, upon rehydration, formed MPC-/lipid A-liposomes (MLLs) with a size under 300 nm and antigen association rates of around 36%. The MLLs given to mice via oral mucosal (o.m.) administration showed no side effects but induced potent immune responses as evidenced by the high levels of IgG in the sera and IgA in the salivary, intestinal and vaginal secretions of mice. High levels of IgG2a and IFN-γ in treated mice revealed that MLLs via o.m. vaccination induced a mixed Th1/Th2 response against antigens, establishing both humoral and cellular immunity. Thus, the MLLs may be a potent cold chain-free oral mucosal vaccine adjuvant-delivery system.

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