PROPERTIES OF PERTUSSIS TOXIN MUTANT PT-9K/129G AFTER FORMALDEHYDE TREATMENT

被引:77
作者
NENCIONI, L
VOLPINI, G
PEPPOLONI, S
BUGNOLI, M
DEMAGISTRIS, T
MARSILI, I
RAPPUOLI, R
机构
关键词
D O I
10.1128/IAI.59.2.625-630.1991
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Formaldehyde treatment is a method routinely used to detoxify diphtheria, tetanus, and pertussis toxins as well as other molecules suitable for vaccine production. To investigate whether chemical detoxification alters the immunological properties of vaccine components, we have treated the pertussis toxin mutant PT-9K/129G with formaldehyde and tested the properties of the resulting molecules. Very low concentrations of formaldehyde stabilize the molecule without affecting the physicochemical and immunological parameters. Increasing doses of formaldehyde abolish the mitogenic and hemagglutinating activities of PT-9K/129G. At the same time, the molecule loses the ability to be recognized by a monoclonal antibody specific for a major protective epitope on the S1 subunit of pertussis toxin and its affinity for anti-pertussis toxin polyclonal antibodies is also reduced. In marked contrast, the ability of PT-9K/129G to be recognized by human T-cell clones is not affected by Formalin treatment. In vivo, the formaldehyde-treated molecules induce amounts of specific antibodies comparable with those of untreated molecules but significantly lower levels of toxin-neutralizing antibodies. Furthermore, the formaldehyde-treated molecules also show a reduced protective activity in the intracerebral challenge assay.
引用
收藏
页码:625 / 630
页数:6
相关论文
共 20 条
  • [1] DISSECTING HUMAN T-CELL RESPONSES AGAINST BORDETELLA SPECIES
    DEMAGISTRIS, MT
    ROMANO, M
    NUTI, S
    RAPPUOLI, R
    TAGLIABUE, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 168 (04) : 1351 - 1362
  • [2] HUMAN T-CELL CLONES DEFINE S1 SUBUNIT AS THE MOST IMMUNOGENIC MOIETY OF PERTUSSIS TOXIN AND DETERMINE ITS EPITOPE MAP
    DEMAGISTRIS, MT
    ROMANO, M
    BARTOLONI, A
    RAPPUOLI, R
    TAGLIABUE, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (05) : 1519 - 1532
  • [3] THE STANDARDIZATION OF AN ASSAY FOR PERTUSSIS TOXIN AND ANTITOXIN IN MICROPLATE CULTURE OF CHINESE-HAMSTER OVARY CELLS
    GILLENIUS, P
    JAATMAA, E
    ASKELOF, P
    GRANSTROM, M
    TIRU, M
    [J]. JOURNAL OF BIOLOGICAL STANDARDIZATION, 1985, 13 (01): : 61 - &
  • [4] Glenny AT, 1923, BRIT J EXP PATHOL, V4, P283
  • [5] NEUTRALIZING ANTIBODIES TO PERTUSSIS TOXIN IN WHOOPING-COUGH
    GRANSTROM, M
    GRANSTROM, G
    GILLENIUS, P
    ASKELOF, P
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1985, 151 (04) : 646 - 649
  • [6] PERTUSSIS TOXIN ANALOG WITH REDUCED ENZYMATIC AND BIOLOGICAL-ACTIVITIES IS A PROTECTIVE IMMUNOGEN
    KIMURA, A
    MOUNTZOUROS, KT
    SCHAD, PA
    CIEPLAK, W
    COWELL, JL
    [J]. INFECTION AND IMMUNITY, 1990, 58 (10) : 3337 - 3347
  • [7] CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4
    LAEMMLI, UK
    [J]. NATURE, 1970, 227 (5259) : 680 - +
  • [8] LOWRY OH, 1951, J BIOL CHEM, V193, P265
  • [9] DETERMINATION OF ANTIGEN-SPECIFIC IMMUNOGLOBULIN CONTENT IN ASCITIC FLUIDS AND ANTISERA
    MARIANI, M
    NUCCI, D
    BRACCI, L
    NERI, P
    ANTONI, G
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 92 (02) : 189 - 193
  • [10] CHARACTERIZATION OF GENETICALLY INACTIVATED PERTUSSIS TOXIN MUTANTS - CANDIDATES FOR A NEW VACCINE AGAINST WHOOPING-COUGH
    NENCIONI, L
    PIZZA, M
    BUGNOLI, M
    DEMAGISTRIS, T
    DITOMMASO, A
    GIOVANNONI, F
    MANETTI, R
    MARSILI, I
    MATTEUCCI, G
    NUCCI, D
    OLIVIERI, R
    PILERI, P
    PRESENTINI, R
    VILLA, L
    KREEFTENBERG, JG
    SILVESTRI, S
    TAGLIABUE, A
    RAPPUOLI, R
    [J]. INFECTION AND IMMUNITY, 1990, 58 (05) : 1308 - 1315