Affinity chromatography of tetanus toxin, tetanus toxoid, and botulinum a toxin on synaptosomes, and differentiation of their acceptors

1976 ◽  
Vol 293 (1) ◽  
pp. 1-9 ◽  
Author(s):  
E. Habermann
Keyword(s):  
Affinity Chromatography ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Botulinum A Toxin

scholarly journals A Novel High-Potency Tetanus Vaccine

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Amanda Przedpelski ◽  
William H. Tepp ◽  
Sabine Pellett ◽  
Eric A. Johnson ◽  
Joseph T. Barbieri
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Receptor Binding ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Full Length ◽  
Microbial Pathogens ◽  
Content Type ◽  
Tetanus Vaccine ◽  
Outbred Mice

ABSTRACT Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of Clostridium tetani proteins, and the active component is present in variable and sometimes minor percentages of vaccine mass. Recombinant production of a genetically inactivated tetanus vaccine offers an opportunity to replace and improve the current tetanus vaccine. Previous studies showed the feasibility of engineering full-length tetanus toxin (TT) in Escherichia coli. In the present study, full-length TT was engineered with eight individual amino acid mutations (8MTT) to inactivate catalysis, translocation, and host receptor-binding functions, retaining 99.4% amino acid identity to native tetanus toxin. 8MTT purified as a 150-kDa single-chain protein, which trypsin nicked to a 100-kDa heavy chain and 50-kDa light chain. The 8MTT was not toxic for outbred mice and was >50 million-fold less toxic than native TT. Relative to CITT, 8MTT vaccination elicited a strong immune response and showed good vaccine potency against TT challenge. The strength of the immune response to both vaccines varied among individual outbred mice. These data support 8MTT as a candidate vaccine against tetanus and a malleable candidate conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules to facilitate a rapid response to emerging microbial pathogens. IMPORTANCE Chemical inactivation is a clinically effective mechanism to detoxify protein toxins to produce vaccines against microbial infections and to serve as a platform for production of conjugate polysaccharide vaccines. This method is widely used for the production of protein toxin vaccines, including tetanus toxoid. However, chemical modification alters the protein structure with unknown effects on antigenicity. Here, a recombinant full-length tetanus toxin (TT) is engineered with 8 mutations (8MTT) that inactivate three toxin functions: catalysis, translocation, and receptor binding. 8MTT is nontoxic and elicits a potent immune response in outbred mice. 8MTT also represents a malleable platform for the production of conjugate vaccines, which can facilitate a rapid vaccine response against emerging microbial pathogens.

Induction of Protection against Tetanus Toxin in Mice by Tetanus Toxoid–Liposome Conjugate

1998 ◽  
Vol 116 (3) ◽  
pp. 215-219 ◽  
Author(s):  
Seishiro Naito ◽  
Atsuko Horino ◽  
Takako Komiya ◽  
Tadashi Fukuda ◽  
Motohide Takahashi ◽  
...  
Keyword(s):  
Tetanus Toxoid ◽  
Tetanus Toxin

scholarly journals Surface topography of histidine residues of tetanus toxin probed by immobilized-metal-ion affinity chromatography

1992 ◽  
Vol 285 (1) ◽  
pp. 9-12 ◽  
Author(s):  
O Rossetto ◽  
G Schiavo ◽  
P Polverino de Laureto ◽  
S Fabbiani ◽  
C Montecucco
Keyword(s):  
Affinity Chromatography ◽  
Heavy Chain ◽  
Light Chain ◽  
Efficient Method ◽  
Tetanus Toxin ◽  
Metal Ion ◽  
Histidine Residues ◽  
Botulinum Neurotoxins ◽  
Matrix Bound ◽  
Metal Ion Affinity Chromatography

Tetanus toxin contains 14 histidine residues: six of them are localized in the light chain (L), one is present in the N-terminal half of the heavy chain (HN) and the remaining seven histidines are localized in the C-terminal half of the heavy chain (Hc). Using immobilized-metal-ion affinity chromatography with Chelating Superose-Zn(II), we show that histidines of Hc are exposed to the protein surface and are responsible for the binding of tetanus toxin and of Hc to the immobilized metal. The histidines of the L chain are not available for co-ordination of matrix-bound Zn2+; however, two of them and three of the histidines of fragment Hc are accessible to diethyl pyrocarbonate. Chromatography on Superose-Zn(II) is also shown to be a simple and efficient method for the rapid isolation of tetanus toxin and of its Hc fragment, which can be extended to the botulinum neurotoxins.

Residual enzymatic activity of the tetanus toxin light chain present in tetanus toxoid batches used for vaccine production

Vaccine ◽  
2008 ◽  
Vol 26 (31) ◽  
pp. 3835-3841 ◽  
Author(s):  
H.A. Behrensdorf-Nicol ◽  
B. Kegel ◽  
U. Bonifas ◽  
K. Silberbach ◽  
J. Klimek ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Light Chain ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Vaccine Production

Nano-sized Soluplus® polymeric micelles enhance the induction of tetanus toxin neutralising antibody response following transcutaneous immunisation with tetanus toxoid

Vaccine ◽  
2017 ◽  
Vol 35 (18) ◽  
pp. 2489-2495 ◽  
Author(s):  
Manolya Saydam ◽  
Woei Ping Cheng ◽  
Nathan Palmer ◽  
Robert Tierney ◽  
Robert Francis ◽  
...  
Keyword(s):  
Antibody Response ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Polymeric Micelles

A CORRELATION BETWEEN THE SPECIFIC PRECOCIOUS PROTECTIVE ACTION AND THE ANTIGENIC RESPONSE OF TETANUS TOXOIDS

1962 ◽  
Vol 8 (4) ◽  
pp. 525-532
Author(s):  
John L. Morrison
Keyword(s):  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Protective Action ◽  
Inhibitory Effect ◽  
Toxic Action

The inhibitory effect of large doses of tetanus toxoid on the toxic action of tetanus toxin varies for different toxoids and this variation parallels the antigenicities of the toxoids. Five toxoids having a range of relative antigenicities from 0.32 to 1.89 were tested. It was found that the more antigenic the toxoid was, the more it interfered with the toxicity.

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