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Pathogenicity and Virulence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Diphtheria toxin, an example of an A-B toxin, is produced by C. diphtheriae. The toxin is a single-chain polypeptide which catalyzes the transfer of adenine diphosphate dinucleotide from nicotinamide dinucleotide to elongation factor 2, resulting in inhibition of protein synthesis. Diphtheria formerly caused very high morbidity and mortality among young children, but since the incorporation of diphtheria toxoid into the Diphtheria-Pertussis-Tetanus (DPT) vaccine the incidence of this disease has been drastically reduced. Other A-B toxins include Shiga toxin of S. dysenteriae, exotoxin A of P. aeruginosa, tetanus toxin of C. tetani, and botulinum toxin of C. botulinum.
Vaccinations
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Joshua H. Barash, Edward M. Buchanan
Tdap vaccine (tetanus toxoid, reduced inactivated diphtheria toxoid, and acellular pertussis) was first licensed in 2005 and now recommended for use in persons age ≥ 7 years old (Table 40.1). Pertussis protection was added to Td vaccine due to a resurgence of pertussis cases worldwide. Family members with pertussis are the source of infection in 75% of cases in early infancy, when complications and fatalities are high [27]. Infants less than 12 months old account for most of the morbidity and mortality related to pertussis [28].
Antigen Delivery Systems Used to Induce Immunomodulation
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
M. Zahirul I. Khan, Ian G. Tucker, Joan P. Opdebeeck
The practice of using aluminum-based gels as immunoadjuvants is as old as the history of adjuvants themselves. In 1926, Glenny et al. [10] first reported the adjuvant activity of alum-precipitated diphtheria toxoid (DT). Antigen either precipitated with alum (KA1SO4.12H2O) or adsorbed onto preformed aluminum gels (aluminum hydroxide or phosphate) possesses enhanced immunological effects. The gelling property of these systems and adsorption of the antigen to the gels prolong the retention of the antigen and its deposition at injection sites. The aluminum gels produce granulomas containing antibody-producing plasma cells, induce chronic inflammation at injection sites, and activate production of cytokines, all of which are supposed to contribute to their adjuvant effects.
A review of the DTaP-IPV-HB-PRP-T Hexavalent vaccine in pediatric patients
Published in Expert Review of Vaccines, 2023
Andrew Dakin, Ray Borrow, Peter D. Arkwright
The vaccines differ slightly in their composition, with DT3aP-IPV-Hib-HBVhaving a higher quantity of diphtheria toxoid (DT) (≥30IU) compared with both DT2aP-IPV-Hib-HBV and Vaxelis (≥20IU). DT2aP-IPV-Hib-HBV targets only two pertussis antigens (PT and FHA), whereas DT3aP-IPV-Hib-HBVtargets three and Vaxelis targets five. In some regions where Pertussis is still a large cause of morbidity and mortality, wP is recommended despite the risk of paralysis, due to its superior immunological protection. Children who received aP vaccines containing only three pertussis antigens such as DT3aP-IPV-Hib-HBV, were more likely to be diagnosed with pertussis than those who received wP containing vaccines. In addition, those who received aP vaccines with five pertussis antigens, such as Vaxelis, showed a similar risk of contracting pertussis compared with wP [59]. It would be beneficial for more comparisons to be made with DT2aP-IPV-Hib-HBV and wP containing vaccines to determine if the risk of contracting pertussis is higher due to DT2aP-IPV-Hib-HBV only containing two pertussis antigens.
Review of scientific evidence to support recommendations of the full-dose DTaP-IPV vaccination in pre-school age children in Italy
Published in Expert Review of Vaccines, 2022
Angela Bechini, Beatrice Zanella, Benedetta Bonito, Paolo Bonanni, Sara Boccalini
A study carried out in Italy in 2000 has shown that children who had received the pediatric dose DT vaccine (25 Lf of diphtheria toxoid and 10 Lf tetanus toxoid per dose) or the low dose dT (2 Lf of diphtheria toxoid and 10 Lf tetanus toxoid per dose) as booster at school-entry age had a similar side-reaction frequency. Only local redness and swelling were significantly more frequent among the DT group [48]. All the enrolled subjects were found to have protective antibodies titers against diphtheria (>0.01 IU/ml, basic protection) and tetanus (≥1 IU/ml, long-term protection) after the booster dose. The post-booster GMT of diphtheria antibodies in the DT group was twice as high as in the dT group (14.1 IU/ml vs 7.7 IU/ml) and this difference was statistically significant (p < 0.001). On the other hand, the post-booster GMT of tetanus antibodies were comparable between the groups (dT: 14.09 IU/ml; DT: 14.08 IU/ml) [48].
Overcoming scientific barriers in the transition from in vivo to non-animal batch testing of human and veterinary vaccines
Published in Expert Review of Vaccines, 2021
Robin H. G. A. van den Biggelaar, Marcel H.N. Hoefnagel, Rob J. Vandebriel, Arjen Sloots, Coenraad F.M. Hendriksen, Willem van Eden, Victor P. M. G. Rutten, Christine A. Jansen
To test for residual toxicity of toxoid vaccines in vitro alternatives have been developed including the Chinese hamster ovary (CHO) cell clustering assay as an alternative to the in vivo Histamine Sensitization Test (HIST) for acellular pertussis vaccines [47]. In addition, a VERO cell toxicity assay has been developed and implemented for specific toxicity testing of diphtheria toxoid vaccines as an alternative to the in vivo test in guinea pigs [48]. Furthermore, a VERO cell toxicity assay to be used instead of the mouse toxicity test for veterinary Clostridium septicum vaccines is currently being validated [49]. Finally, the binding and cleavage (BINACLE) assay evaluates residual tetanus toxicity of toxoid bulk that is produced for human and veterinary tetanus vaccines, as an alternative for the currently used test in guinea pigs [50]. The BINACLE assay is currently being validated as part of the European Biological Standardization Programme. Unfortunately, the BINACLE assay cannot be used for vaccine final products that contain tetanus toxoid in an adjuvant-adsorbed state [50].