期刊
VACCINE
卷 32, 期 42, 页码 5475-5483出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.07.081
关键词
Liposome vaccine; Lymphatic targeting; Immunological memory; Germinal center; Follicular T helper cells
资金
- National Natural Science Foundation of China [81171446, 81371679]
- Guangdong Innovation Research Team Fund for Low-cost Healthcare Technologies (GIRTF-LCHT)
- Key Project of Science and Technology of Guangdong [2012B090400043, 2012B090600036]
- Shenzhen Science and Technology Program [JC201005260247A, CXZZ20130506140505859]
- Nanshan Innovative Technology Program [KC2013JSJS0012A]
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. (C) 2014 Elsevier Ltd. All rights reserved.
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