The mucosa is the primary point of entry for pathogens making it an important vaccination site to produce a protective mucosal immune response. While the sublingual (SL) mucosa presents several barriers to
vaccine penetration, its unique anatomy and physiology makes it one of the best options for mucosal vaccination. Efficient and directed delivery of adjuvants and
antigens to appropriate immune mediators in the SL tissue will aid in development of effective SL
vaccines against
infectious diseases. Herein we demonstrate a robust immune response against
influenza antigens co-delivered sublingually with engineered
liposomes carrying the synthetic Toll-like receptor-4 agonist, CRX-601.
Liposome modification with PEG copolymers (
Pluronics),
phospholipid-PEG conjugates and
chitosan were evaluated for their ability to generate an immune response in a SL murine
influenza vaccine model.
Phospholipid-PEG conjugates were more effective than
Pluronic copolymers in generating stable, surface neutral
liposomes. SL vaccination with surface modified
liposomes carrying CRX-601 adjuvant generated significant improvements in flu-specific responses compared with unmodified
liposomes. Furthermore, the coating of modified
liposomes with
methylglycol chitosan produced the most effective flu-specific immune response. These results demonstrate efficient SL
vaccine delivery utilizing a combination of a muco-adhesive and surface neutral
liposomes to achieve a robust mucosal and systemic immune response.