A murine monoclonal antibody produced in transgenic plants with plant-specific glycans is not immunogenic in mice

被引:89
作者
Chargelegue, D [1 ]
Vine, ND [1 ]
van Dolleweerd, CJ [1 ]
Drake, PMW [1 ]
Ma, JKC [1 ]
机构
[1] Guys Hosp, Guys Kings & St Thomas Sch Med & Dent, Dept Oral Med & Pathol, Immunol Unit, London SE1 9RT, England
关键词
immunogenicity; plant glycans; recombinant antibody; therapeutic agents; transgenic plants;
D O I
10.1023/A:1008976219939
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have shown that the production of recombinant antibodies in plants is highly efficient and presents numerous therapeutic applications. It is, however, known that plant glycoproteins display different glycosylation patterns to those exhibited by mammalian glycoproteins. Thus, it is important to know if these plant recombinant antibodies could induce undesirable immune responses in mammal; and to date no report has documented the potential immunogenicity of parenterally administered plant recombinant antibodies in animals. In order to answer this question, mice were immunised subcutaneously with a recombinant mouse monoclonal antibody produced in tobacco plants, together with alum as adjuvant. Two control groups were immunised in the same way with either the original murine monoclonal antibody or horseradish peroxidase (a plant glycoprotein). Analyses by direct immunoassay, competition immunoassay and real-time surface plasmon resonance, showed undetectable levels of antibody directed against both the protein and the glycan part of the plant recombinant antibody. These results have a direct relevance for the application of plant recombinant proteins as therapeutic agents and vaccines in humans.
引用
收藏
页码:187 / 194
页数:8
相关论文
共 24 条
  • [1] THE GLYCOSYLATION OF GLYCOPROTEIN LECTINS - INTRA-GENUS AND INTER-GENUS VARIATION IN N-LINKED OLIGOSACCHARIDE EXPRESSION
    ASHFORD, DA
    DWEK, RA
    RADEMACHER, TW
    LIS, H
    SHARON, N
    [J]. CARBOHYDRATE RESEARCH, 1991, 213 : 215 - 227
  • [2] N-glycosylation of a mouse IgG expressed in transgenic tobacco plants
    Cabanes-Macheteau, M
    Fitchette-Lainé, AC
    Loutelier-Bourhis, C
    Lange, C
    Vine, ND
    Ma, JKC
    Lerouge, P
    Faye, L
    [J]. GLYCOBIOLOGY, 1999, 9 (04) : 365 - 372
  • [3] A peptide mimic of a protective epitope of respiratory syncytial virus selected from a combinatorial library induces virus-neutralizing antibodies and reduces viral load in vivo
    Chargelegue, D
    Obeid, OE
    Hsu, SC
    Shaw, MD
    Denbury, AN
    Taylor, G
    Steward, MW
    [J]. JOURNAL OF VIROLOGY, 1998, 72 (03) : 2040 - 2046
  • [4] THE PLANT GOLGI-APPARATUS - A FACTORY FOR COMPLEX POLYSACCHARIDES AND GLYCOPROTEINS
    DRIOUICH, A
    FAYE, L
    STAEHELIN, LA
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1993, 18 (06) : 210 - 214
  • [5] AFFINITY PURIFICATION OF ANTIBODIES SPECIFIC FOR ASN-LINKED GLYCANS CONTAINING ALPHA-1-]3 FUCOSE OR BETA-1-]2 XYLOSE
    FAYE, L
    GOMORD, V
    FITCHETTELAINE, AC
    CHRISPEELS, MJ
    [J]. ANALYTICAL BIOCHEMISTRY, 1993, 209 (01) : 104 - 108
  • [6] Francis DP, 1998, AIDS RES HUM RETROV, V14, pS325
  • [7] Immunogenicity of two doses of yeast recombinant hepatitis B vaccine in healthy older adults
    Gellin, BG
    Greenberg, RN
    Hart, RH
    Bertino, JS
    Stein, DH
    Deloria, MA
    ClementsMann, ML
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1997, 175 (06) : 1494 - 1497
  • [8] Hiatt A, 1993, Int Rev Immunol, V10, P139, DOI 10.3109/08830189309061691
  • [9] PRODUCTION OF ANTIBODIES IN TRANSGENIC PLANTS
    HIATT, A
    CAFFERKEY, R
    BOWDISH, K
    [J]. NATURE, 1989, 342 (6245) : 76 - 78
  • [10] Synergistic effect of immunization with a peptide cocktail inducing antibody, helper and cytotoxic T-cell responses on protection against respiratory syncytial virus
    Hsu, SC
    Chargelegue, D
    Obeid, OE
    Steward, MW
    [J]. JOURNAL OF GENERAL VIROLOGY, 1999, 80 : 1401 - 1405