Practice question

Toxoid vaccines prevent disease caused by potent bacterial exotoxins rather than bacterial invasion itself. Diphtheria toxin 58 kDa AB toxin ADP-ribosylates elongation factor eEF2 halting protein synthesis causing myocardial necrosis, neuritis; tetanus toxin tetanospasmin 150 kDa metalloprotease cleaves VAMP synaptobrevin preventing inhibitory neurotransmitter release causing spastic paralysis. Native toxins lethal at nanogram per kg doses far too dangerous for direct use. Formaldehyde formalin approximately 37 percent formaldehyde aqueous solution discovered by Gaston Ramon 1923 to detoxify toxin preserving immunogenicity. Mechanism involves cross linking lysine residues via hydroxymethyl intermediates forming methylene bridges disrupting catalytic site while preserving conformational epitopes recognized by neutralizing antibodies. Incubation with 0.2-0.6 percent formalin at 37°C pH 6-7 for several weeks converts toxin to toxoid losing toxicity but retaining ability to induce antitoxin antibodies that bind toxin preventing attachment to receptors. Verification by lack of toxicity in guinea pig challenge assay and absence of residual free formaldehyde. Toxoid adsorbed to aluminum salts generates long lasting IgG antitoxin, cornerstone of diphtheria tetanus control since 1920s, eliminating former leading causes childhood mortality.