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Disease relevance of Tetanus

  • BACKGROUND: The administration of the diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine has been associated with adverse neurologic events, including seizures [1].
  • The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM197 (Oligo-CRM) [2].
  • Functional analysis of the unreactive (TH1-) and reactive (TH1+) T-cell subclasses demonstrated that TH1- cells mounted a good proliferative response to a battery of specific soluble antigens (mumps, PPD, tetanus toxoid) but neither responded in MLC, nor elaborated LMF in response to tetanus toxoid [3].
  • Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid [4].
  • To study the role of such disease-associated epitopes in antigen-restricted T cell recognition we generated T cell clones from RA patients specific for mycobacterial antigens, Epstein-Barr virus antigens, and tetanus toxoid [5].

Psychiatry related information on Tetanus


High impact information on Tetanus

  • This antigen-specific effect could be generalized to another DR1-restricted peptide, Tetanus toxoid 830-843 [11].
  • In an animal model of acute promyelocytic leukemia, we developed a DNA-based vaccine by fusing the human promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) oncogene to tetanus fragment C (FrC) sequences [12].
  • A TrkB-IgG fusion protein, which scavenges endogenous BDNF, reduced the synaptic responses to tetanus as well as the magnitude of LTP in adult hippocampus [13].
  • NMDA receptors initiate a molecular event that needs to be triggered each time a tetanus is delivered to induce LTP [14].
  • Recently tetanus toxin was shown to proteolytically degrade synaptobrevin II (also named VAMP-2), a synaptic vesicle-specific protein, in vitro and in nerve terminals [15].

Chemical compound and disease context of Tetanus

  • A rise in similarly positive T cells occurred in normal individuals after immunization with tetanus toxoid or PPD [16].
  • Tetanus toxin reduced neuronal injury produced by brief exposure to elevated extracellular K+ or to glutamate, situations in which release of endogenous excitatory neurotransmitter is likely to play a role [17].
  • Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin [17].
  • To determine the time for which Ca2+ must remain elevated to induce LTP, the photolabile Ca2+ buffer diazo-4 was used to limit the duration of the rise in postsynaptic [Ca2+]i following a tetanus [18].
  • The three vaccine components included HBV core antigen peptide 18-27 as the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids [19].

Biological context of Tetanus


Anatomical context of Tetanus


Gene context of Tetanus

  • We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen [30].
  • VAMP2 in kidney membranes was cleaved by tetanus toxin, revealing a tetanus toxin-sensitive VAMP homologue [31].
  • Similarly, tetanus toxin cleaved VAMP2 in synaptic vesicles [31].
  • Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1 [32].
  • Correspondingly, only synaptobrevin (n-syb), but not the ubiquitously expressed syb protein, is cleaved by tetanus toxin in vitro [33].

Analytical, diagnostic and therapeutic context of Tetanus


  1. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. Barlow, W.E., Davis, R.L., Glasser, J.W., Rhodes, P.H., Thompson, R.S., Mullooly, J.P., Black, S.B., Shinefield, H.R., Ward, J.I., Marcy, S.M., DeStefano, F., Chen, R.T., Immanuel, V., Pearson, J.A., Vadheim, C.M., Rebolledo, V., Christakis, D., Benson, P.J., Lewis, N. N. Engl. J. Med. (2001) [Pubmed]
  2. Avidity and bactericidal activity of antibody elicited by different Haemophilus influenzae type b conjugate vaccines. The Vaccine Study Group. Schlesinger, Y., Granoff, D.M. JAMA (1992) [Pubmed]
  3. Detection, isolation, and functional characterization of two human T-cell subclasses bearing unique differentiation antigens. Evans, R.L., Breard, J.M., Lazarus, H., Schlossman, S.F., Chess, L. J. Exp. Med. (1977) [Pubmed]
  4. Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types. Berzofsky, J.A., Pendleton, C.D., Clerici, M., Ahlers, J., Lucey, D.R., Putney, S.D., Shearer, G.M. J. Clin. Invest. (1991) [Pubmed]
  5. Disease-associated human histocompatibility leukocyte antigen determinants in patients with seropositive rheumatoid arthritis. Functional role in antigen-specific and allogeneic T cell recognition. Weyand, C.M., Goronzy, J.J. J. Clin. Invest. (1990) [Pubmed]
  6. Past exposure to vaccines and subsequent risk of Alzheimer's disease. Verreault, R., Laurin, D., Lindsay, J., De Serres, G. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. (2001) [Pubmed]
  7. Determining indications for adult vaccination: patient self-assessment, medical record, or both? Fishbein, D.B., Willis, B.C., Cassidy, W.M., Marioneaux, D., Bachino, C., Waddington, T., Wortley, P. Vaccine (2006) [Pubmed]
  8. The stereotyped behavior syndrome: a new model and proposed therapy. Kryzhanovsky, G.N., Aliev, M.N. Pharmacol. Biochem. Behav. (1981) [Pubmed]
  9. Developmental neuroplasticity: roles in early life seizures and chronic epilepsy. Swann, J.W., Pierson, M.G., Smith, K.L., Lee, C.L. Advances in neurology. (1999) [Pubmed]
  10. Fracture-dislocation of manubriosternal joint: an unusual complication of seizures. Dastgeer, G.M., Mikolich, D.J. The Journal of trauma. (1987) [Pubmed]
  11. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. De Magistris, M.T., Alexander, J., Coggeshall, M., Altman, A., Gaeta, F.C., Grey, H.M., Sette, A. Cell (1992) [Pubmed]
  12. PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Padua, R.A., Larghero, J., Robin, M., le Pogam, C., Schlageter, M.H., Muszlak, S., Fric, J., West, R., Rousselot, P., Phan, T.H., Mudde, L., Teisserenc, H., Carpentier, A.F., Kogan, S., Degos, L., Pla, M., Bishop, J.M., Stevenson, F., Charron, D., Chomienne, C. Nat. Med. (2003) [Pubmed]
  13. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Figurov, A., Pozzo-Miller, L.D., Olafsson, P., Wang, T., Lu, B. Nature (1996) [Pubmed]
  14. A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation. Bortolotto, Z.A., Bashir, Z.I., Davies, C.H., Collingridge, G.L. Nature (1994) [Pubmed]
  15. Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein. McMahon, H.T., Ushkaryov, Y.A., Edelmann, L., Link, E., Binz, T., Niemann, H., Jahn, R., Südhof, T.C. Nature (1993) [Pubmed]
  16. Peripheral blood Ia-positive T cells. Increases in certain diseases and after immunization. Yu, D.T., Winchester, R.J., Fu, S.M., Gibofsky, A., Ko, H.S., Kunkel, H.G. J. Exp. Med. (1980) [Pubmed]
  17. Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin. Monyer, H., Giffard, R.G., Hartley, D.M., Dugan, L.L., Goldberg, M.P., Choi, D.W. Neuron (1992) [Pubmed]
  18. Temporal limits on the rise in postsynaptic calcium required for the induction of long-term potentiation. Malenka, R.C., Lancaster, B., Zucker, R.S. Neuron (1992) [Pubmed]
  19. Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. Vitiello, A., Ishioka, G., Grey, H.M., Rose, R., Farness, P., LaFond, R., Yuan, L., Chisari, F.V., Furze, J., Bartholomeuz, R. J. Clin. Invest. (1995) [Pubmed]
  20. A cell-free system for regulated exocytosis in PC12 cells. Avery, J., Ellis, D.J., Lang, T., Holroyd, P., Riedel, D., Henderson, R.M., Edwardson, J.M., Jahn, R. J. Cell Biol. (2000) [Pubmed]
  21. The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Bruggemann, H., Baumer, S., Fricke, W.F., Wiezer, A., Liesegang, H., Decker, I., Herzberg, C., Martinez-Arias, R., Merkl, R., Henne, A., Gottschalk, G. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  22. T-Cell immune reconstitution in pediatric leukemia patients after allogeneic bone marrow transplantation with T-cell-depleted or unmanipulated grafts: evaluation of overall and antigen-specific T-cell repertoires. Godthelp, B.C., van Tol, M.J., Vossen, J.M., van Den Elsen, P.J. Blood (1999) [Pubmed]
  23. Immunological memory to tetanus toxoid is established and maintained in the vitamin A-depleted rat. Kinoshita, M., Pasatiempo, A.M., Taylor, C.E., Ross, A.C. FASEB J. (1991) [Pubmed]
  24. Inhibition of transmitter release correlates with the proteolytic activity of tetanus toxin and botulinus toxin A in individual cultured synapses of Hirudo medicinalis. Bruns, D., Engers, S., Yang, C., Ossig, R., Jeromin, A., Jahn, R. J. Neurosci. (1997) [Pubmed]
  25. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Blasi, J., Chapman, E.R., Link, E., Binz, T., Yamasaki, S., De Camilli, P., Südhof, T.C., Niemann, H., Jahn, R. Nature (1993) [Pubmed]
  26. Human monoclonals from antigen-specific selection of B lymphocytes and transformation by EBV. Casali, P., Inghirami, G., Nakamura, M., Davies, T.F., Notkins, A.L. Science (1986) [Pubmed]
  27. VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx. Singh, B.B., Lockwich, T.P., Bandyopadhyay, B.C., Liu, X., Bollimuntha, S., Brazer, S.C., Combs, C., Das, S., Leenders, A.G., Sheng, Z.H., Knepper, M.A., Ambudkar, S.V., Ambudkar, I.S. Mol. Cell (2004) [Pubmed]
  28. Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues. Xu-Amano, J., Kiyono, H., Jackson, R.J., Staats, H.F., Fujihashi, K., Burrows, P.D., Elson, C.O., Pillai, S., McGhee, J.R. J. Exp. Med. (1993) [Pubmed]
  29. Urushiol (poison ivy)-triggered suppressor T cell clone generated from peripheral blood. Kalish, R.S., Morimoto, C. J. Clin. Invest. (1988) [Pubmed]
  30. Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15. Seder, R.A., Grabstein, K.H., Berzofsky, J.A., McDyer, J.F. J. Exp. Med. (1995) [Pubmed]
  31. Expression of VAMP-2-like protein in kidney collecting duct intracellular vesicles. Colocalization with Aquaporin-2 water channels. Nielsen, S., Marples, D., Birn, H., Mohtashami, M., Dalby, N.O., Trimble, M., Knepper, M. J. Clin. Invest. (1995) [Pubmed]
  32. Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. Locksley, R.M., Crowe, S., Sadick, M.D., Heinzel, F.P., Gardner, K.D., McGrath, M.S., Mills, J. J. Clin. Invest. (1988) [Pubmed]
  33. Targeted expression of tetanus toxin light chain in Drosophila specifically eliminates synaptic transmission and causes behavioral defects. Sweeney, S.T., Broadie, K., Keane, J., Niemann, H., O'Kane, C.J. Neuron (1995) [Pubmed]
  34. Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. Rathjen, F.G., Schachner, M. EMBO J. (1984) [Pubmed]
  35. Properties of neurons from dissociated fetal rat brain in serum-free culture. Ahmed, Z., Walker, P.S., Fellows, R.E. J. Neurosci. (1983) [Pubmed]
  36. Development of Thy-1 antigen on cerebellar neurons in culture. Fields, K.L., Currie, D.N., Dutton, G.R. J. Neurosci. (1982) [Pubmed]
  37. Proteins and their derived peptides as carriers in a conjugate vaccine for Streptococcus pneumoniae: self-heat shock protein 60 and tetanus toxoid. Amir-Kroll, H., Nussbaum, G., Cohen, I.R. J. Immunol. (2003) [Pubmed]
  38. Tetanus vaccination with IL-2 during highly active antiretroviral therapy induces sustained and pronounced specific CD4 T-cell responses. Hardy, G.A., Imami, N., Sullivan, A.K., Nelson, M.R., Gazzard, B., Gotch, F.M. AIDS (2004) [Pubmed]
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