Lymphatic-targeted liposome vaccines promote long-term immunological memory (VAC10P.963)

Abstract

Abstract Lymphatic-targeted vaccine delivery with liposome formulations has been reported to enhance the immunogenicity of vaccines. However, its effect on long-term immunological memory remains unclear. In the present study, OVA vaccines were formulated by cationic liposomes with different surface modification: DOTAP liposomes (LP), PEGylated DOTAP (LP-PEG) liposomes, and mannosylated DOTAP (LP-Man) liposomes. The in vivo imaging showed that LP mostly accumulated near the injection site, indicating its depot effect. In contrast, LP-PEG and LP-Man liposomes effectively accumulated in draining lymph nodes and the spleen, indicating their lymphatic targeting. More importantly, different liposomes differentially regulate antibody response and B-cell memory. Although LP vaccine led to the highest level of anti-OVA IgG among three liposome formulations on day 40 post priming, they failed to establish an effective memory response. In contrast, lymphatic-targeted LP-PEG and LP-Man vaccines elicited sustained antibody response and robust recall responses 3 months after priming. The enhanced long-term immunological memory by lymphatic-targeted liposome vaccines could be attributed to vigorous and persistent germinal center response, as well as increased Tfh cells and central memory CD4+ T cells in the spleen and lymph nodes. Hence, lymphatic-targeted vaccine delivery with surface modified cationic liposomes could be an effective strategy to promote long-lasting immunological memory.