New insights in formaldehyde-induced detoxification of the tetanus toxin: Chemical modification stoichiometry and characterization of intra- and inter-molecular cross-links

The active ingredient of the tetanus vaccine, known as tetanus toxoid (TTD, 150 kDa), is prepared by inactivation of the tetanus toxin with formaldehyde. This chemical treatment determines the efficiency and innocuity of the vaccine. The detoxification chemistry has been qualitatively studied regarding the nature and positioning of some formaldehyde-induced modifications. However, neither the stoichiometry of the chemical modifications or intra- and inter-chain cross-linking have been yet characterized, despite being of great interest for the definitive elucidation of the detoxification mechanism as well as for future manufacturing follow-up. The aim of the present study is to assess the impact of formaldehyde on TTD by identifying, mapping, and quantifying as exhaustively as possible, all formaldehyde-induced modifications over the entire three-dimensional (3D) structure of the protein. Please click Download on the upper right corner to see the full abstract

The combined use of analytical tools for exploring tetanus toxin and tetanus toxoid structures

International audienc