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 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.

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.

scholarly journals Production of tetanus toxin by using media substantially free from meat and blood

2016 ◽  
Vol 9 (6) ◽  
pp. 284
Author(s):  
Dr. Anil Kumar Chawla ◽  
Chandrani Das ◽  
Paramdeep Singh ◽  
Mansha Tiwari ◽  
Dr. Seema Chaudhary
Keyword(s):  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Scale Up ◽  
Casein Hydrolysate ◽  
Toxin Production ◽  
Optimum Conditions ◽  
Fractional Precipitation ◽  
Clostridium Tetani ◽  
Post Vaccination ◽  
Free Media

The present study was to redesign the conventional Mueller and Miller medium to produce tetanus toxin from Clostridium tetani. Meat based ingredients (such as Bovine Heart/ Brain/ Liver Infusion) were replaced with vegetable peptone & alternate casein hydrolysate and scaled up from 100mL to 1000mL. Modified Mueller and Miller Medium containing vegetable peptone (substitute of BHI) and alternate casein hydrolysate were used for production and scale -up of tetanus toxin. Detoxification of tetanus toxin was carried out by using formaldehyde to produce tetanus toxoid. Purification of tetanus toxoid was achieved by fractional precipitation. It was found that under optimum conditions, use of meat free media leads to production of tetanus toxin with equal limes flocculation (Lf) titer and high antigenic content at par with conventional meat based media without any post vaccination infections. The yield of toxin was improved during scale-up of the process. The present study provides a method for growth of Clostridium tetani that maximizes tetanus toxin production without any use of animal-derived components.

scholarly journals Transcutaneous delivery of tetanus toxin Hc fragment induces superior tetanus toxin neutralizing antibody response compared to tetanus toxoid

2009 ◽  
Vol 5 (4) ◽  
pp. 230-236 ◽  
Author(s):  
Louise Johnston ◽  
Fatme Mawas ◽  
Rob Tierney ◽  
Omar Qazi ◽  
Neil Fairweather ◽  
...  
Keyword(s):  
Antibody Response ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Neutralizing Antibody ◽  
Transcutaneous Delivery

scholarly journals Influence of preimmunization with tetanus toxoid on immune responses to tetanus toxin fragment C-guest antigen fusions in a Salmonella vaccine carrier.

1995 ◽  
Vol 63 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
J A Chabalgoity ◽  
B Villareal-Ramos ◽  
C M Khan ◽  
S N Chatfield ◽  
R D de Hormaeche ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Vaccine Carrier

scholarly journals Comparison of the Abilities of Different AttenuatedSalmonella typhimurium Strains To Elicit Humoral Immune Responses against a Heterologous Antigen

1998 ◽  
Vol 66 (2) ◽  
pp. 732-740 ◽  
Author(s):  
Sarah J. Dunstan ◽  
Cameron P. Simmons ◽  
Richard A. Strugnell
Keyword(s):  
Immune Response ◽  
Tetanus Toxoid ◽  
Tetanus Toxin ◽  
Lethal Dose ◽  
Antigen Expression ◽  
Oral Immunization ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Heterologous Antigen ◽  
Interleukin 5

ABSTRACT We compared the abilities of different Salmonella enterica var. Typhimurium (S. typhimurium) strains harboring mutations in the genes aroA, aroAD,purA, ompR, htrA, and cya crp to present the heterologous antigen, C fragment of tetanus toxin, to the mouse immune system. Plasmid pTETtac4, encoding C fragment, was transferred into the various S. typhimuriummutants, and the levels of antigen expression were found to be equivalent. After primary oral immunization of BALB/c mice, all attenuated strains were capable of penetrating the gut epithelium and colonizing the Peyer’s patches and spleens of mice. Of all strains compared, the ΔpurA mutant colonized and persisted in the Peyer’s patches at the lowest level, whereas the ΔhtrAmutant colonized and persisted in the spleen at the lowest level. The level of specific antibody elicited by the different strains against either S. typhimurium lipopolysaccharide or tetanus toxoid was strain dependent and did not directly correlate to the mutants’ ability to colonize the spleen. The level of immunoglobulin G1 (IgG1) and IgG2a antibody specific for tetanus toxoid was determined in mice immunized with four S. typhimurium mutants. The level of antigen-specific IgG1 and IgG2a was significantly lower in animals immunized with S. typhimurium ΔpurA. Antigen-specific T-cell proliferation assays indicated a degree of variability in the capacity of some strains to elicit T cells to the heterologous antigen. Cytokine profiles (gamma interferon and interleukin-5) revealed that the four S. typhimuriummutants tested induced a Th1-type immune response. Mice were challenged with a lethal dose of tetanus toxin 96 days after oral immunization. With the exception of the S. typhimuriumΔpurA mutant, all strains elicited a protective immune response. These data indicate that the level of total Ig specific for the carried antigen, C fragment, does not correlate with the relative invasiveness of the vector, but it is determined by the carrier mutation and the background of the S. typhimurium strain.

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