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E J Wiertz

Publications and source records attributed to E J Wiertz.

20 records · Page 2Linked to original sources

Acellular and whole cell pertussis vaccines protect against the lethal effects of intracerebral challenge by two different T-cell dependent humoral routes.

Athymic (nu/nu) and euthymic (+/nu) BALB/c mice were immunized with a whole cell pertussis vaccine or with an acellular vaccine which contained detoxified pertussis toxin (PT) and filamentous hemagglutinin (FHA). Only the euthymic mice were protected against intracerebral challenge with virulent Bordetella pertussis which implies involvement of T-cells. As a cell transfer from mice immunized with whole cell or acellular vaccine prior to the challenge did not protect naive euthymic recipients, cellular immunity seems to be non-protective as an effector mechanism. Mice could be protected passively against a challenge by administration of immune sera. Therefore, T-cell dependent humoral immune responses to B. pertussis appear to be crucial for protection. The humoral response was further studied with athymic and euthymic mice. In euthymic mice the whole cell vaccine induced antibodies to FHA, pililipopolysaccharides (LPS) and an outer membrane protein (OMP) preparation, whereas the acellular vaccine induced antibodies to PT, FHA and OMP. Both IgM and IgG could be detected. From the nude mice only those immunized with the whole cell vaccine showed an antibody response which consisted of low titres of IgM directed to LPS. Sera from both +/nu and nu/nu mice immunized with the whole cell vaccine were bactericidal in vitro. These data demonstrate that in the mouse model protection to intracerebral challenge with B. pertussis is T-cell dependent as is the humoral response to PT, FHA, OMP and pili. The T-independent B-cell activation by the whole cell preparation is due to the presence of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro induction of antigen specific antibody synthesis and proliferation of T lymphocytes with acellular pertussis vaccines, pertussis toxin and filamentous haemagglutinin in humans.

The in vitro response of human B- and T-lymphocytes to the acellular vaccines JNIH-6 (containing pertussis toxoid and filamentous hemagglutinin), and JNIH-7 (containing pertussis toxoid), and to the purified components JNIH-4 (filamentous hemagglutinin) and JNIH-5 (pertussis toxin) was investigated. Pertussis toxoid and filamentous hemagglutinin induced specific Ig synthesis in vitro in lymphocytes obtained from convalescent pertussis patients as target cells. The antigen-dependent Ig production was demonstrated in lymphocyte culture supernatants by ELISA techniques and by a chinese hamster ovary cell toxin neutralization assay. Particularly with JNIH-4, -6 and -7, high antibody titers were obtained. At optimal antigen concentrations a marked lymphocyte blast transformation was found in lymphocyte cultures from whooping cough patients, but not in cultures of lymphocytes obtained from healthy volunteers. At high concentrations native pertussis toxin as well as the B oligomer (S2-5) of the toxin induced a strong proliferation of patient as well as control lymphocytes, indicating non-specific mitogenic activity. At lower concentrations lymphocyte blast transformation was seen in patient cultures only, which indicates an antigen-specific T-cell response. The A protomer (S1), dimer 1 (S2 + 4) and dimer 2 (S3 + 4) induced proliferation of patient lymphocytes, which demonstrates the presence of T-cell epitopes on these peptides. The in vitro B-cell response and the lymphocyte blast transformation assay are both useful tools for estimating the potency of acellular pertussis vaccines in man. Spontaneously acquired and vaccine induced immunity to Bordetella pertussis can be investigated at the level of B- and T-lymphocytes.

Antibody Formation↗