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Genetically detoxified pertussis toxin (PTgen) is a recombinant protein derived from the primary virulence factor of Bordetella pertussis, the bacterium responsible for whooping cough (Pizza et al., 1989, Science). In its native form, pertussis toxin is an AB5-type exotoxin that catalyzes the ADP-ribosylation of inhibitory G proteins, leading to a range of systemic pathologies (UniProt P04977). The genetically detoxified version is engineered with specific point mutations, most commonly Arg9Lys and Glu129Gly, which completely abolish the toxin's enzymatic activity while preserving its complex quaternary structure (EMA, 2023, Pertagen Assessment Report). This structural integrity is crucial because it maintains the native conformational epitopes required for the induction of high-quality neutralizing antibodies. Unlike chemically detoxified toxins, which can undergo structural distortion and potential reversion to toxicity, PTgen provides a safer and more immunogenic alternative for acellular pertussis vaccines. It is currently used in clinical applications to provide robust, long-lasting protection against pertussis by stimulating both humoral and cellular immune memory (Podda et al., 1991, Vaccine).
Acts as a vaccine antigen that induces the production of neutralizing antibodies and memory T-cells by presenting native-like conformational epitopes of the pertussis toxin without the associated ADP-ribosyltransferase toxicity.
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