PEGylated cationic liposomes robustly augment vaccine-induced immune responses: Role of lymphatic trafficking and biodistribution.
Lymph nodes (LNs) are peripheral lymphoid organs essential for vaccine-induced immune responses. Although cationic liposomes have been documented as a novel adjuvant and vaccine delivery system, whether enhancing LN targeting would improve the efficiency of cationic liposome-formulated vaccines has not been elucidated yet. In the present study we investigated the effect of PEGylation on LN targeting and the immunogenicity of cationic liposome-formulated vaccines. DOTAP cationic liposomes were incorporated with 1 or 5mol% of DSPE-PEG2000 and labeled with near infrared fluorescent dyes. The lymphatic trafficking and biodistribution of different liposomes after subcutaneous (s.c.) injection were recorded using an in-vivo imaging system. The results showed that incorporation of 1mol% DSPE-PEG2000 not only accelerated the drainage of DOTAP liposomes into draining LNs, but also prolonged their LN retention and enhanced liposome uptake by resident antigen-presenting cells. On the other hand, although incorporating 5mol% of DSPE-PEG2000 into DOTAP liposomes enhanced their LN retention and uptake to a lesser extent, it prolonged blood circulation of DOTAP liposomes and increased their splenic accumulation. In addition, PEGylated DOTAP liposomes augmented primary and secondary anti-OVA antibody responses more potently than nonPEGylated DOTAP liposomes did. Hence, incorporating a small amount of DSPE-PEG2000 into DOTAP liposomes not only increased the passive LN targeting of DOTAP-formulated vaccines but also modulated their biodistribution in vivo, which consequently improved the efficiency of cationic liposome-formulated vaccines.
Key Lab of Health Informatics of Chinese Academy of Sciences, Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advance Technology, Chinese Academy of Science, People's Republic of China.
Yan
Y
Zhuang
Yifan
Y
Ma
Ce
C
Wang
Luo
L
Hai
Chao
C
Yan
Yijuan
Y
Zhang
Fengzhi
F
Liu
Lintao
L
Cai
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry*; D014018:Tissue Distribution; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000276:Adjuvants, Immunologic; D000941:Antigens; D005229:Fatty Acids, Monounsaturated; D007074:Immunoglobulin G; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; D011092:Polyethylene Glycols; D010047:Ovalbumin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane