Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough.
AUTOR(ES)
Nencioni, L
RESUMO
the introduction of two amino acid substitutions within the enzymatically active subunit S1 of pertussis toxin (PT) abolishes its ADP-ribosyltransferase activity and toxicity on CHO cells (Pizza et al., Science 246:497-500, 1989). These genetically inactivated molecules are also devoid of other in vivo adverse reactions typical of PT, such as induction of leukocytosis, potentiation of anaphylaxis, stimulation of insulin secretion, and histamine sensitivity. However, the mutant PT molecules are indistinguishable from wild-type PT in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and maintain all the physical and chemical properties of PT, including affinity for toxin-neutralizing poly- and monoclonal antibodies. Either alone or stabilized with formaldehyde, PT mutants are able to induce high levels of neutralizing antibodies and to protect mice in a dose-dependent fashion against intracerebral challenge with virulent B. pertussis. These results clearly show that these genetically inactivated PT molecules are nontoxic but still immunogenic and justify their development as a component of a new, safer acellular vaccine against whooping cough.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=258625Documentos Relacionados
- Engineering of genetically detoxified pertussis toxin analogs for development of a recombinant whooping cough vaccine.
- Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough.
- Evaluation of serologic assays for diagnosis of whooping cough.
- Counterimmunoelectrophoresis in the diagnosis of whooping cough.
- H. PERTUSSIS VACCINE IN THE PROPHYLAXIS AND THERAPY OF WHOOPING COUGH