期刊
VACCINE
卷 28, 期 14, 页码 2598-2606出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.01.013
关键词
Sublingual route; Mucosal vaccination; Human papillomavirus; Sublingual adjuvant
资金
- Korea government [R01-2007-000-20475-0)]
- Health and Medical Technology RD program [A092010, A090945]
- Bio-Green 21 program [20070501-034-001-009-03-00]
- Rural Development Administration, South Korea
- National Research Foundation of Korea [R01-2007-000-20475-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Needle-free nonparenteral vaccines offer a number of practical advantages, especially in developing countries. To address the effects of vaccine administration route, we tested mucosal and systemic immune responses against human papillomavirus 16 L1(HPV16L1) protein using intranasal, intravaginal, transdermal, sublingual (SL) and intramuscular routes. The SL route provided the most effective mucosal secretory IgA (sIgA) and serum IgG responses. After a 15014 antigen dose via the SL route, saliva sIgA levels were 7.2- and 5.8-fold higher than those achieved via intravaginal and transdermal routes, respectively. Notably, SL administration even produced 4.6-fold higher levels of vaginal sIgA levels than did intravaginal delivery of 150 mu g antigen. To enhance the immunogenicity of SL vaccines, we tested the adjuvanticity of nine molecules: three toll-like receptor agonists, three nucleotide-binding oligomerization-domain agonists, vitamin D3, poly-gamma-glutamic acid and cholera toxin subunit B (CTB). Among the molecules tested, CTB provided the most enhanced mucosal sIgA and systemic IgG induction. SL-applied CTB enhanced the production of interleukin-4 and interferon-gamma from stimulated CD4+ T cells. Moreover, interferon-gamma-producing CD8+ T cell responses were increased 1.7-fold after co-treatment with SL CTB and HPV16L1. These results suggest the potential of the SL route for delivery of HPV16L1 vaccines using CTB as an adjuvant. (C) 2010 Elsevier Ltd. All rights reserved.
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