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

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.

1991 ◽  
Vol 173 (6) ◽  
pp. 1305-1310 ◽  
Author(s):  
M Gadina ◽  
R Bertini ◽  
M Mengozzi ◽  
M Zandalasini ◽  
A Mantovani ◽  
...  

The present study was designed to define the potential of chlorpromazine (CPZ) as a protective agent against lipopolysaccharide (LPS) toxicity in comparison with glucocorticoids, and to obtain initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxic shock. It was found that CPZ protects mice, normal or adrenalectomized, and guinea pigs against lethality of LPS, and inhibited TNF serum levels, like dexamethasone (DEX), a well-known inhibitor of TNF synthesis. CPZ protected against LPS lethality when administered 30 minutes (min) before, simultaneously, or up to 10 min after LPS and was ineffective when given 30 min after LPS, paralleling the inhibitory effect on TNF production. In another experimental model, where mice were sensitized to LPS toxicity by actinomycin D, CPZ significantly inhibited LPS lethality and hepatotoxicity, whereas under these conditions DEX was inactive. These experiments indicate that CPZ has a protective action in both glucocorticoid-sensitive and -resistant models of endotoxic shock.


1954 ◽  
Vol 86 (3) ◽  
pp. 545-548 ◽  
Author(s):  
L. Goldman ◽  
T. B. Turner ◽  
E. S. Stafford

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Amanda Przedpelski ◽  
William H. Tepp ◽  
Sabine Pellett ◽  
Eric A. Johnson ◽  
Joseph T. Barbieri

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.


1977 ◽  
Vol 162 (1) ◽  
pp. 9-18 ◽  
Author(s):  
L Å Idahl ◽  
Å Lernmark ◽  
J Sehlin ◽  
I B Täljedal

Exposing micro-dissected pancreatic islets of non-inbred ob/ob mice to 2-5 mM-alloxan for 10 min decreased the ability of the islets to accumulate Rb+. Rb+ accumulation in pieces of exocrine pancreas was unaffected by alloxan. When islets were treated with alloxan in the presence of 2-20 mM-D-glucose, the Rb+-accumulating ability was protected in a dose-dependent manner. The protective action of D-glucose was reproduced with 3-O-methyl-D-glucose but not with L-glucose or D-mannoheptulose; mannoheptulose prevented D-glucose from exerting its protective action. The inhibition of Rb+ accumulation was due to a decreased inward pumping, since alloxan did not affect Rb+ efflux from pre-loaded islets. The inhibitory effect of alloxan had a latency of about 1 min, as revealed by experiments with dispersed islet cells in suspension. Alloxan-treated islets showed only a marginal decrease in ATP and no change in glucose 6-phosphate concentration. Although alloxan slightly decreased the hydrolysis of ATP in a subcellular fraction enriched in plasma membranes, this effect could not be attributed to a ouabain-sensitive adenosine triphosphatase. The plasma membranes exhibited a K+-activated hydrolysis of p-nitrophenyl phosphate; this enzyme activity too was insensitive to alloxan. Glucose may protect the univalent-cation pump by preventing permeation of alloxan via a path coupled to the hexose-transport system. Inhibition of the pump may be fundamental to the induction of alloxan-diabetes.


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

Vaccine ◽  
2008 ◽  
Vol 26 (31) ◽  
pp. 3835-3841 ◽  
Author(s):  
H.A. Behrensdorf-Nicol ◽  
B. Kegel ◽  
U. Bonifas ◽  
K. Silberbach ◽  
J. Klimek ◽  
...  

Vaccine ◽  
2017 ◽  
Vol 35 (18) ◽  
pp. 2489-2495 ◽  
Author(s):  
Manolya Saydam ◽  
Woei Ping Cheng ◽  
Nathan Palmer ◽  
Robert Tierney ◽  
Robert Francis ◽  
...  

2019 ◽  
Vol 62 (1) ◽  
pp. 345-351 ◽  
Author(s):  
Adam Tarko ◽  
Aneta Štochmal'ová ◽  
Katarína Jedličková ◽  
Sandra Hrabovszká ◽  
Adriana Vachanová ◽  
...  

Abstract. We hypothesized that the environmental contaminant benzene and the plant antioxidant quercetin may affect ovarian cell functions and that quercetin could offer protection against the adverse effects of benzene. This study aimed to examine the action of benzene, quercetin, and their combination on porcine ovarian granulosa cell functions. We elucidated the effects of benzene (20 µg mL−1), quercetin (at the doses 0, 1, 10, 100 µg mL−1), and their combination on ovarian granulosa cell functions (proliferation, apoptosis, and hormone release) in vitro using immunocytochemistry and enzyme immunoassay respectively. Benzene alone stimulated proliferation, apoptosis, and oxytocin release and inhibited progesterone and prostaglandin F release. Quercetin alone inhibited proliferation, apoptosis, and stimulated oxytocin release but did not affect progesterone and prostaglandin F release. When used in combination with benzene, quercetin promoted the inhibitory effect of benzene on progesterone release. Overall, these data suggest that benzene and quercetin have direct stimulatory and inhibitory effects, respectively, on basic ovarian functions. Moreover, no protective action of quercetin against the effects of benzene was found. Rather, it was found to enhance the effect of benzene on progesterone release. Therefore, quercetin cannot be considered for preventing or mitigating the effects of benzene on reproductive processes.


Author(s):  
Dr. Anil Kumar Chawla ◽  
Chandrani Das ◽  
Paramdeep Singh ◽  
Mansha Tiwari ◽  
Dr. Seema Chaudhary

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.


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