![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Pertussis toxin (PT) is one of the major virulence factors of Bordetella pertussis and the primary component of all pertussis vaccines available to date. Because of its various noxious effects the toxin needs to be detoxified. In all currently available vaccines, detoxification is achieved by treatment with high quantity of chemical agents such as formaldehyde, glutaraldehyde or hydrogen peroxide. Although effective in detoxification, this chemical treatment alters dramatically the immunological properties of the toxin. In contrast, PT genetically detoxified through the substitution of two residues necessary for its enzymatic activity maintains all functional and immunological properties. This review describes in detail the characteristics of this PT-9K/129G mutant and shows that it is non-toxic and a superior immunogen compared with chemically detoxified PT. Importantly, data from an efficacy trial show that the PT-9K/129G-based vaccine induces earlier and longer-lasting protection, further supporting the hypothesis that PT-9K/129G represents an ideal candidate for future pertussis vaccine formulations.
Acknowledgements
The authors wish to thank G Corsi for graphic work.
Financial & competing interests disclosure
The authors are employees of Novartis Vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Only genetic inactivation of pertussis toxin (PT) leads to a completely safe vaccine antigen that maintains important immunogenic epitopes and intrinsic adjuvant capacity.
In contrast, chemical PT inactivation is inversely correlated with immunogenicity, and the risk that some molecules can revert to toxicity persists.
Genetically inactivated PT-9K/129G has been shown to be an effective vaccine antigen and adjuvant when administered by systemic or mucosal routes.
Vaccines containing genetically inactivated PTg outperformed vaccines containing chemically inactivated PTd in preclinical infection models even when lower antigen doses were used.
The added value of genetic inactivation of PT has been confirmed in clinical trials.