title: Lymphatic-targeted cationic liposomes: a robust vaccine adjuvant for promoting long-term immunological memory.
abstract: Although retaining antigens at the injection site (the so-called "depot effect") is an important strategy for vaccine development, increasing evidence showed that lymphatic-targeted vaccine delivery with liposomes could be a promising approach for improving vaccine efficacy. However, it remains unclear whether antigen depot or lymphatic targeting would benefit long-term immunological memory, a major determinant of vaccine efficacy. In the present study, OVA antigen was encapsulated with DOTAP cationic liposomes (LP) or DOTAP-PEG-mannose liposomes (LP-Man) to generate depot or lymphatic-targeted liposome vaccines, respectively. The result of in vivo imaging showed that LP mostly accumulated near the injection site, whereas LP-Man not only effectively accumulated in draining lymph nodes (LNs) and the spleen, but also enhanced the uptake by resident antigen-presenting cells. Although LP vaccines with depot effect induced anti-OVA IgG more potently than LP-Man vaccines did on day 40 after priming, they failed to mount an effective B-cell memory response upon OVA re-challenge after three months. In contrast, lymphatic-targeted LP-Man vaccines elicited sustained antibody production and robust recall responses three months after priming, suggesting lymphatic targeting rather than antigen depot promoted the establishment of long-term memory responses. The enhanced long-term immunological memory by LP-Man was attributed to vigorous germinal center responses as well as increased Tfh cells and central memory CD4(+) T cells in the secondary lymphoid organs. Hence, lymphatic-targeted vaccine delivery with LP-Man could be an effective strategy to promote long-lasting immunological memory.
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Ce
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Boling
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen 518055, PR China. Electronic address: yf.ma@siat.ac.cn.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D018858:Germinal Center / Q000276:immunology; D007156:Immunologic Memory; D008081:Liposomes / Q000737:chemistry*; D008198:Lymph Nodes / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014612:Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D008081:Liposomes; D014612:Vaccines; D010047:Ovalbumin
keywords: Follicular T helper cells; Germinal center; Immunological memory; Liposome vaccine; Lymphatic targeting