More than a Toxin: Protein Inventory of Clostridium tetani Toxoid Vaccines

Abstract

Clostridium tetani is the etiological agent of tetanus, a life-threatening bacterial infection. The most efficient protection strategy against tetanus is a vaccination with the C. tetani neurotoxin, which is inactivated by formaldehyde-crosslinking. Since we assumed that besides the tetanus toxin, other proteins of C. tetani may also be present in toxoid preparations, we analyzed commercially available vaccines from different countries in respect to their protein content using mass spectrometry. In total 991 proteins could be identified in all five analyzed vaccines, 206 proteins were common in all analyzed vaccines and 54 proteins from the 206 proteins were potential antigens. The additionally present proteins may contribute at least partially to protection against C. tetani infection by supporting the function of the vaccine against the devastating effects of the tetanus toxin indirectly. Two different label-free protein quantification methods were applied for an estimation of protein contents. Similar results were obtained with a Total Protein Approach (TPA)-based method and Protein Discoverer 2.2 software package based on the minora algorithm. Depending on the tetanus toxoid vaccine and the quantification method used, tetanus neurotoxin contributes between 14 and 76 % to the total C. tetani protein content and varying numbers of other C. tetani proteins were detected.

Potential Cross-Reactive Immunity to SARS-CoV-2 From Common Human Pathogens and Vaccines

“…After considering the nature of bacterial vaccines, we discarded conjugate and polysaccharides vaccines and sought for potential sources of cross-reactive immunity in antigens identified by proteomics in DTa/wP and MenB vaccines. D and T antigens can vary between different vaccines, and here we considered the sum of all those reported elsewhere in (13,14,49). Our results, summarized in Table 4, indicate that combination DTP vaccines are significant sources of B and T cell cross-reactivity to SARS-CoV-2, while such cross-reactivity is small from MenB vaccine.…”

“…In contrast, vaccines for N. meningitides serotype B (MenB) consist of surface proteins from N. meningitides (15). Diphteria (D) and tetanus (T) vaccines contain inactivated toxins produced by the bacteria (toxoids) but in addition include a large array of proteins as shown by proteomics studies, which can be immunogenic (14,49). D and T antigens are generally combined with pertussis (P) antigens as a combination DTP vaccine, which is available in two main formulations: DTaP and DTwP.…”

A Novel High-Potency Tetanus Vaccine

“…Current CITT vaccines are clinically effective but are crude and contain varied amounts of CITT (7). Mass spectrometric analyses of five human CITT vaccines identified 991 C. tetani proteins, of which 206 proteins were common to the five vaccines (7).…”

“…3) (0.1 g in alum) followed by one boost of 8MTT or CITT (0.1 g in alum). Enzyme-linked immunosorbent assay (ELISA) assessment of IgG in blood collected at Przedpelski et al 7 days postboost showed that 8MTT and CITT elicited similar IgG responses to those of the antigens used in the ELISA, which included TT Ͼ light chain (LC) linked to the translocation domain (HCN) (LCHCN) ϭ HCC Ͼ LC. Six of eight mice vaccinated with one boost of 8MTT and five of eight mice vaccinated with one boost of CITT survived challenge by 10,000ϫ LD 50 i.p.…”

“…vaccine is crude and possesses varied amounts of CITT (7). In addition, CITT vaccination can be clinically reactive, leading to unwanted side effects after injection (8).…”