Direct intralymphatic injection of peptide vaccines enhances immunogenicity

被引:108
作者
Johansen, P
Häffner, AC
Koch, E
Zepter, K
Erdmann, L
Maloy, K
Simard, JJ
Storni, T
Senti, G
Bot, A
Wüthrich, B
Kündig, TM
机构
[1] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland
[2] MannKind Corp, Valencia, NM USA
关键词
vaccination; CTL; peptide; virus; route of administration;
D O I
10.1002/eji.200425599
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Research to enhance the efficiency of vaccines focuses mainly on improving either the adjuvant or the type and form of the antigen. This study evaluates the influence of the administration route on the efficiency of a peptide-based vaccine. Peptide vaccines are generally administered subcutaneously or intradermally, from where they must reach secondary lymphatic organs to induce an immune response. We analyzed the efficacy of peptide vaccines administered directly into a lymph node. Using a MHC class I-binding peptide from lymphocytic choriomeningitis virus, we found that intralymphatic injection enhanced immunogenicity by as much as 106 times when compared to subcutaneous and intradermal vaccination. Intralymphatic administration induced CD8 T cell responses with strong cytotoxic activity and IFN-gamma production that conferred long-term protection against viral infections and tumors. These results should have immediate implications for clinical immunotherapy of infectious disease and cancer.
引用
收藏
页码:568 / 574
页数:7
相关论文
共 17 条
[1]  
BINDER D, 1991, J IMMUNOL, V146, P4301
[2]   Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells [J].
Dhodapkar, MV ;
Steinman, RM ;
Sapp, M ;
Desai, H ;
Fossella, C ;
Krasovsky, J ;
Donahoe, SM ;
Dunbar, PR ;
Cerundolo, V ;
Nixon, DF ;
Bhardwaj, N .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (02) :173-180
[3]   CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor vaccine efficacy [J].
Diehl, L ;
den Boer, AT ;
Schoenberger, SP ;
van der Voort, EIH ;
Schumacher, TNM ;
Melief, CJM ;
Offringa, R ;
Toes, REM .
NATURE MEDICINE, 1999, 5 (07) :774-779
[4]   Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells [J].
Hsu, FJ ;
Benike, C ;
Fagnoni, F ;
Liles, TM ;
Czerwinski, D ;
Taidi, B ;
Engleman, EG ;
Levy, R .
NATURE MEDICINE, 1996, 2 (01) :52-58
[5]   CpG motifs in bacterial DNA and their immune effects [J].
Krieg, AM .
ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 :709-760
[6]   FIBROBLASTS AS EFFICIENT ANTIGEN-PRESENTING CELLS IN LYMPHOID ORGANS [J].
KUNDIG, TM ;
BACHMANN, MF ;
DIPAOLO, C ;
SIMARD, JJL ;
BATTEGAY, M ;
LOTHER, H ;
GESSNER, A ;
KUHLCKE, K ;
OHASHI, PS ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
SCIENCE, 1995, 268 (5215) :1343-1347
[7]   Intralymphatic immunization enhances DNA vaccination [J].
Maloy, KJ ;
Erdmann, I ;
Basch, V ;
Sierro, S ;
Kramps, TA ;
Zinkernagel, RM ;
Oehen, S ;
Kündig, TM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3299-3303
[8]   Bone marrow-derived dendritic cells serve as potent adjuvants for peptide-based antitumor vaccines [J].
Mayordomo, JI ;
Zorina, T ;
Storkus, WJ ;
Zitvogel, L ;
GarciaPrats, MD ;
DeLeo, AB ;
Lotze, MT .
STEM CELLS, 1997, 15 (02) :94-103
[9]   VIRAL ESCAPE BY SELECTION OF CYTOTOXIC T-CELL-RESISTANT VIRUS VARIANTS INVIVO [J].
PIRCHER, H ;
MOSKOPHIDIS, D ;
ROHRER, U ;
BURKI, K ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
NATURE, 1990, 346 (6285) :629-633
[10]   N-PROTEIN IS THE PREDOMINANT ANTIGEN RECOGNIZED BY VESICULAR STOMATITIS VIRUS-SPECIFIC CYTOTOXIC-T CELLS [J].
PUDDINGTON, L ;
BEVAN, MJ ;
ROSE, JK ;
LEFRANCOIS, L .
JOURNAL OF VIROLOGY, 1986, 60 (02) :708-717