MUTANTS OF ESCHERICHIA-COLI HEAT-LABILE TOXIN LACKING ADP-RIBOSYLTRANSFERASE ACTIVITY ACT AS NONTOXIC, MUCOSAL ADJUVANTS

被引：236
作者：
DOUCE, G
TURCOTTE, C
CROPLEY, I
ROBERTS, M
PIZZA, M
DOMENGHINI, M
RAPPUOLI, R
DOUGAN, G
机构：
[1] UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,VACCINE RES UNIT,LONDON SW7 2AZ,ENGLAND
[2] IRIS,I-53100 SIENA,ITALY
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1995年 / 92卷 / 05期
关键词：
HEAT-LABILE ENTEROTOXIN; NONTOXIC MUTANT; TETANUS;
D O I：
10.1073/pnas.92.5.1644
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
A nontoxic mutant (LTK7) of the Escherichia coli heat-labile enterotoxin (LT) lacking ADP-ribosylating activity but retaining holotoxin formation was constructed. By using site-directed mutagenesis, the arginine at position 7 of the A subunit was replaced with lysine. This molecule, which was nontoxic in several assays, was able to bind to eukaryotic cells and acted as a mucosal adjuvant for co-administered proteins; BALB/c mice immunized intranasally with LTK7 and ovalbumin developed high levels of serum and local antibodies to ovalbumin and toxin. In addition, mice immunized intranasally with fragment C of tetanus toxin and LTK7 were protected against lethal challenge with tetanus toxin. Thus nontoxic mutants of heat-labile toxin can act as effective intranasal mucosal adjuvants.
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页码：1644 / 1648
页数：5
相关论文
共 21 条
  • [11] OPTIMIZING ORAL VACCINES - INDUCTION OF SYSTEMIC AND MUCOSAL B-CELL AND ANTIBODY-RESPONSES TO TETANUS TOXOID BY USE OF CHOLERA-TOXIN AS AN ADJUVANT
    JACKSON, RJ
    FUJIHASHI, K
    XUAMANO, JC
    KIYONO, H
    ELSON, CO
    MCGHEE, JR
    [J]. INFECTION AND IMMUNITY, 1993, 61 (10) : 4272 - 4279
  • [12] LIPSCOMBE M, 1991, MOL MICROBIOL, V5, P1385
  • [13] EFFECT OF SITE-DIRECTED MUTAGENIC ALTERATIONS ON ADP-RIBOSYLTRANSFERASE ACTIVITY OF THE A-SUBUNIT OF ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN
    LOBET, Y
    CLUFF, CW
    CIEPLAK, W
    [J]. INFECTION AND IMMUNITY, 1991, 59 (09) : 2870 - 2879
  • [14] THE ADJUVANT EFFECT OF VIBRIO-CHOLERAE AND ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXINS IS LINKED TO THEIR ADP-RIBOSYLTRANSFERASE ACTIVITY
    LYCKE, N
    TSUJI, T
    HOLMGREN, J
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (09) : 2277 - 2281
  • [15] THE MUCOSAL IMMUNE-SYSTEM - FROM FUNDAMENTAL-CONCEPTS TO VACCINE DEVELOPMENT
    MCGHEE, JR
    MESTECKY, J
    DERTZBAUGH, MT
    ELDRIDGE, JH
    HIRASAWA, M
    KIYONO, H
    [J]. VACCINE, 1992, 10 (02) : 75 - 88
  • [16] MOWAT AM, 1994, HDB MUCOSAL IMMUNOLO, P185
  • [17] CURRENT PROGRESS IN THE DEVELOPMENT OF THE B-SUBUNITS OF CHOLERA-TOXIN AND ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN AS CARRIERS FOR THE ORAL DELIVERY OF HETEROLOGOUS ANTIGENS AND EPITOPES
    NASHAR, TO
    AMIN, T
    MARCELLO, A
    HIRST, TR
    [J]. VACCINE, 1993, 11 (02) : 235 - 240
  • [18] STRUCTURE AND FUNCTION OF CHOLERA-TOXIN AND THE RELATED ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN
    SPANGLER, BD
    [J]. MICROBIOLOGICAL REVIEWS, 1992, 56 (04) : 622 - 647
  • [19] SVENNERHOLM AM, 1993, J CURR MICROBIOL, V1, P19
  • [20] ADJUVANT ACTION OF CHOLERA-TOXIN AND PERTUSSIS TOXIN IN THE INDUCTION OF IGA ANTIBODY-RESPONSE TO ORALLY-ADMINISTERED ANTIGEN
    WILSON, AD
    ROBINSON, A
    IRONS, L
    STOKES, CR
    [J]. VACCINE, 1993, 11 (02) : 113 - 118
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