Acid-degradable particles for protein-based vaccines:: Enhanced survival rate for tumor-challenged mice using ovalbumin model

被引:67
作者
Standley, SM
Kwon, YJ
Murthy, N
Kunisawa, J
Shastri, N
Guillaudeu, SJ
Lau, L
Fréchet, JMJ [1 ]
机构
[1] Univ Calif Berkeley, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA
[4] Lawrence Berkeley Lab, Div Mat Sci, Berkeley, CA 94720 USA
关键词
D O I
10.1021/bc049956f
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Acid-degradable protein-loaded polymer particles show promise for antigen-based vaccines due to their ability to activate cytotoxic T lymphocytes (CTLs) in vitro. Protein loadings and cytotoxic T lymphocyte activation efficiencies have now been enhanced through novel delivery vehicle designs. In particular, the use of a more hydrophilic acid-degradable cross-linker leads to increased water dispersibility and increased protein loading efficiency for the particles. A 2.5-fold increase in protein encapsulation allows the delivery of more protein antigen to antigen presenting cells (APCs) leading to a 20-fold rise in antigen presentation levels. The mechanism by which APCs internalize these particles was explored using the phagocytosis inhibitor, cytochalasin B. In addition, preliminary in vivo experiments were conducted to investigate the ability of the protein-loaded particles to provide immunity against tumors in mice, and an enhanced survival rate over the use of protein alone was observed, indicating that this vaccine delivery strategy has great practical potential.
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收藏
页码:1281 / 1288
页数:8
相关论文
共 30 条
[1]   Strategies for designing and optimizing new generation vaccines [J].
Berzofsky, JA ;
Ahlers, JD ;
Belyakov, IM .
NATURE REVIEWS IMMUNOLOGY, 2001, 1 (03) :209-219
[2]   Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety [J].
Blower, SM ;
Koelle, K ;
Kirschner, DE ;
Mills, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3618-3623
[3]   Efficient gene delivery into human dendritic cells by adenovirus polyethylenimine and mannose polyethylenimine transfection [J].
Diebold, SS ;
Lehrmann, H ;
Kursa, M ;
Wagner, E ;
Cotten, M ;
Zenke, M .
HUMAN GENE THERAPY, 1999, 10 (05) :775-786
[4]  
EDMAN P, 1980, J PHARM SCI-US, V69, P838, DOI 10.1002/jps.2600690725
[5]   INCORPORATION OF MACROMOLECULES IN MICROPARTICLES - PREPARATION AND CHARACTERISTICS [J].
EKMAN, B ;
LOFTER, C ;
SJOHOLM, I .
BIOCHEMISTRY, 1976, 15 (23) :5115-5120
[6]  
el-Shamil K, 1999, EUR J IMMUNOL, V29, P3295, DOI 10.1002/(SICI)1521-4141(199910)29:10<3295::AID-IMMU3295>3.3.CO
[7]  
2-E
[8]   Dendritic cells in cancer immunotherapy [J].
Fong, L ;
Engleman, EG .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :245-273
[9]   Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes [J].
Fukasawa, M ;
Shimizu, Y ;
Shikata, K ;
Nakata, M ;
Sakakibara, R ;
Yamamoto, N ;
Hatanaka, M ;
Mizuochi, T .
FEBS LETTERS, 1998, 441 (03) :353-356
[10]   HIV-1 Tat protein as a potential AIDS vaccine [J].
Goldstein, G .
NATURE MEDICINE, 1996, 2 (09) :960-964