Starch microparticles as an adjuvant in immunisation:: effect of route of administration on the immune response in mice

被引:24
作者
Stertman, L [1 ]
Strindelius, L [1 ]
Sjöholm, I [1 ]
机构
[1] Uppsala Univ, Dept Pharm, Ctr Biomed, SE-75123 Uppsala, Sweden
关键词
microparticles; vaccine adjuvant; oral immunisation; parenteral immunisation; Th1/Th2; differentiation; mucosal immune response;
D O I
10.1016/j.vaccine.2003.12.019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This paper describes the effects on the development of an immune response by changing the route of administration of a new vaccine adjuvant, starch microparticles with human serum albumin (HSA) as a model antigen. The model vaccine was administered to mice by oral, subcutaneous and intramuscular routes in various combinations and both the local secretory immunoglobulin antibody (s-IgA) and systemic Immoral and cellular (delayed-type hypersensitivity assay (DTH)) responses were followed. The only immunisation regimens inducing a significant s-IgA response were those incorporating oral booster doses. Oral and subcutaneous immunisations had similar effects on the Th1/Th2 balance, as indicated by the IgG subclass ratios and cytokine analyses. However, significant differences between oral and intramuscular immunisations were seen in the IgG subclass ratios. The Th2 influence was stronger after oral primary immunisation than after intramuscular primary immunisation, while oral boosters elicited a comparatively stronger Th1 response than intramuscular boosters. This result was also supported by the DTH analyses. Subcutaneous immunisation induced a stronger Th2 response than intramuscular immunisation, as indicated by subclass ratio and the IgE response. In conclusion, our results show that the profile of an immune response depends on the route of administration, which should be considered when developing new vaccines or new routes of administration. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2863 / 2872
页数:10
相关论文
共 33 条
[1]   Functional diversity of helper T lymphocytes [J].
Abbas, AK ;
Murphy, KM ;
Sher, A .
NATURE, 1996, 383 (6603) :787-793
[2]   Toll-like receptors in the induction of the innate immune response [J].
Aderem, A ;
Ulevitch, RJ .
NATURE, 2000, 406 (6797) :782-787
[3]   Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes, and skin of the mouse [J].
Anjuère, F ;
Martín, P ;
Ferrero, I ;
Fraga, ML ;
del Hoyo, GM ;
Wright, N ;
Ardavin, C .
BLOOD, 1999, 93 (02) :590-598
[4]  
ARTURSSON P, 1984, J PHARM SCI, V73, P1507, DOI 10.1002/jps.2600731103
[5]  
BETHELL GS, 1979, J BIOL CHEM, V254, P2572
[6]   NEW PERSPECTIVES OF CD28-B7-MEDIATED T-CELL COSTIMULATION [J].
BLUESTONE, JA .
IMMUNITY, 1995, 2 (06) :555-559
[7]   GENERATION OF DIVERSITY IN THE HIERARCHY OF T-CELL EPITOPE RESPONSES FOLLOWING DIFFERENT ROUTES OF IMMUNIZATION WITH SIMIAN IMMUNODEFICIENCY VIRUS PROTEIN [J].
BROOKES, R ;
BERGMEIER, LA ;
MITCHELL, E ;
WALKER, J ;
TAO, L ;
KLAVINSKIS, L ;
MEYERS, NJ ;
LAYTON, G ;
ADAMS, SE ;
LEHNER, T .
AIDS, 1995, 9 (09) :1017-1024
[8]   Biodegradable microparticles of influenza viral vaccine: comparison of the effects of routes of administration on the in vivo immune response in mice [J].
Chattaraj, SC ;
Rathinavelu, A ;
Das, SK .
JOURNAL OF CONTROLLED RELEASE, 1999, 58 (02) :223-232
[9]  
CHER DJ, 1987, J IMMUNOL, V138, P3688
[10]   Induction of TH1 and TH2 CD4+ T cell responses: The alternative approaches [J].
Constant, SL ;
Bottomly, K .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :297-322