Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity

被引:73
作者
Bungener, L [1 ]
Huckriede, A [1 ]
de Mare, A [1 ]
de Vries-Idema, J [1 ]
Wilschut, J [1 ]
Daemen, T [1 ]
机构
[1] Univ Groningen, Dept Med Microbiol, Mol Virol Sect, NL-9713 AV Groningen, Netherlands
关键词
virosomes; cytotoxic T lymphocytes; antigen delivery; antigen processing; vaccine development;
D O I
10.1016/j.vaccine.2004.09.002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Induction of CTL responses against protein antigens is an important aim in vaccine development. In this paper we present fusion-active virosomes as a vaccine delivery system capable of efficient induction of CTL responses in vivo. Virosomes are reconstituted viral membranes, which do not contain the genetic material of the virus they are derived from. Foreign macromolecules, including protein antigens, can be encapsulated in virosomes during the reconstitution process. Functionally reconstituted virosomes retain the cell binding and fusion characteristics of the native virus. Thus, upon uptake by cells through receptor-mediated endocytosis, virosomes will deliver their content to the cell cytosol. In a previous study, we demonstrated that protein antigens delivered in this manner to dendritic cells are efficiently processed for both MHC class I and class 11 presentation. Here, we studied in vivo induction of cellular immune responses against virosome-encapsulated ovalbumin (OVA) in mice. As little as 0.75 mug OVA delivered by fusion-active virosomes was sufficient to induce a powerful class I MHC-restricted CTL response. All immunization routes that were used (i.m., i.p. and s.c.) resulted in efficient induction of CTL activity. The CTLs induced were cytotoxic in a standard Cr-51-release assay and produced IFN-gamma in response to OVA peptide. Thus, virosomes represent an ideal antigen delivery system for induction of cellular immunity against encapsulated protein antigens. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1232 / 1241
页数:10
相关论文
共 54 条
  • [1] ALMEIDA JD, 1975, LANCET, V2, P899
  • [2] Induction of cytotoxic T lymphocyte activity by fusion-active peptide-containing virosomes
    Arkema, A
    Huckriede, A
    Schoen, P
    Wilschut, J
    Daemen, T
    [J]. VACCINE, 2000, 18 (14) : 1327 - 1333
  • [3] Dendritic cells and the control of immunity
    Banchereau, J
    Steinman, RM
    [J]. NATURE, 1998, 392 (6673) : 245 - 252
  • [4] INACTIVATED INFLUENZA-VIRUS, WHEN PRESENTED ON DENDRITIC CELLS, ELICITS HUMAN CD8(+) CYTOLYTIC T-CELL RESPONSES
    BENDER, A
    BUI, LK
    FELDMAN, MAV
    LARSSON, M
    BHARDWAJ, N
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) : 1663 - 1671
  • [5] Help for cytotoxic-T-cell responses is mediated by CD40 signalling
    Bennett, SRM
    Carbone, FR
    Karamalis, F
    Flavell, RA
    Miller, JFAP
    Heath, WR
    [J]. NATURE, 1998, 393 (6684) : 478 - 480
  • [6] BOTTCHER CJF, 1961, ANAL CHIM ACTA, V24, P203
  • [7] ROLE OF VIRAL INFECTIVITY IN INDUCTION OF INFLUENZA VIRUS-SPECIFIC CYTOTOXIC T-CELLS
    BRACIALE, TJ
    YAP, KL
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1978, 147 (04) : 1236 - 1252
  • [8] CELLULAR CYTOPLASMIC DELIVERY OF A POLYPEPTIDE TOXIN BY RECONSTITUTED INFLUENZA-VIRUS ENVELOPES (VIROSOMES)
    BRON, R
    ORTIZ, A
    WILSCHUT, J
    [J]. BIOCHEMISTRY, 1994, 33 (31) : 9110 - 9117
  • [9] PREPARATION, PROPERTIES, AND APPLICATIONS OF RECONSTITUTED INFLUENZA-VIRUS ENVELOPES (VIROSOMES)
    BRON, R
    ORTIZ, A
    DIJKSTRA, J
    STEGMANN, T
    WILSCHUT, J
    [J]. METHODS IN ENZYMOLOGY, 1993, 220 : 313 - 331
  • [10] Virosome-mediated delivery of protein antigens to dendritic cells
    Bungener, L
    Serre, K
    Bijl, L
    Leserman, L
    Wilschut, J
    Daemen, T
    Machy, P
    [J]. VACCINE, 2002, 20 (17-18) : 2287 - 2295