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PubMed2000

Anti-tetanus toxoid antibody production and protection against lethal doses of tetanus toxin in hu-PBL-SCID mice.

BACKGROUND: In this study, severe combined immunodeficiency (SCID) mice, which permit the survival of lymphoid cells of human origin, were used to study the human anti-tetanus immune response. METHODS: Human peripheral blood lymphocytes (hu-PBL) obtained from 88 healthy donors (aged from 18 to 62) were transplanted into SCID mice, and anti-tetanus toxoid (Ttd) antibody production and protection against lethal doses of tetanus toxin (Ttx) were investigated in the hu-PBL-SCID mice. RESULTS: The transfer of human PBL evoked significant human anti-Ttd IgG antibody production for 37.5% of the donors. After in vivo immunization, the percentage of donors with PBL exhibiting positive anti-TtD IgG production in the mice increased to 54.5%. Mean anti-Ttd IgG levels in the sera were also significantly elevated in response to immunization. The mean IgG titer for the mice injected with PBL from donors under the age of 40 was significantly higher than that of the mice injected with PBL from donors aged 40 or older. Four weeks after the cell transfer, the mice were challenged with Ttx. The induction of protection against Ttx challenge was observed mostly in mice with PBL transferred from donors under the age of 40. In vivo immunization in SCID mice with Ttd increased the number of cases of resistance to Ttx. CONCLUSIONS: These results suggest that hu-PBL-SCID mice might serve as a tool for predicting the protective ability against pathogens in PBL donors and also for evaluating vaccine efficacy.

Adolescent↗
PubMed2001

Update on the supply of tetanus and diphtheria toxoids and of diphtheria and tetanus toxoids and acellular pertussis vaccine.

During the last quarter of 2000, the U.S. Public Health Service learned of a shortage of tetanus and diphtheria toxoids (Td) and tetanus toxoid (TT) resulting from decreased production of these vaccines by the two U.S. manufacturers. Previously published recommendations outlined priorities for use of the limited supply of Td and TT. The shortage was expected to be resolved by early 2001; however, on January 10, 2001, Wyeth Lederle (Pearl River, New York) announced it had stopped production of tetanus toxoid-containing products. Although a small amount of Td is produced by the University of Massachusetts for local distribution, Aventis Pasteur (Swiftwater, Pennsylvania) is now the sole nationwide distributor of Td and TT. Aventis Pasteur is shipping limited quantities of vaccine to assure a wide distribution of available doses.

Diphtheria Toxoid↗
PubMed1975

Treatment of tetanus in the horse by injections of tetanus antitoxin into the subarachnoid space.

In 40 horses with tetanus, large doses of tetanus antitoxin (TAT) were injected into the subarachnoid space. In all the horses that recovered, the disease stabilized immediately after the injection. The results (77.5% recovery) were much better than in a previous series of horses with tetanus (50% recovery), in which TAT was injected either intravenously, intramuscularly, or in the epidural space.

Animals↗
PubMed1978

[Immune status after tetanus vaccination. Possibilities and indications for a quantitative rapid determination of tetanus antibodies in human serum].

Active and passive immunization against tetanus is one of the most used vaccination procedures in our population. Detection of size and duration of protection till now failed due to expensive methods. Counter-Immuno-Electrophoresis (CIE) is presented as a simple and non-expensive method with adequate sensitivity, and allows to obtain data concerning immunity of tetanus-immunized persons in almost any case. Rarely positive results as to antitoxin level are obtainable only by more sensitive methods. Further detection methods, and examinations of tetanus-immunity of "problem patients" showing immunofailure and of collectives immunized on various schedules will be reported later.

Child↗
PubMed1980

Reduction of neonatal tetanus by mass immunization of non-pregnant women: duration of protection provided by one or two doses of aluminium-adsorbed tetanus toxoid.

Immunization of non-pregnant women in rural Bangladesh with two doses of aluminium-adsorbed tetanus-diphtheria toxoids reduced neonatal mortality by one-third during a period of 9-32 months after vaccination. The reduction in mortality rate was attributable almost entirely to a 75% lower mortality rate among 4-14-day-old infants, when tetanus was the predominant cause of death.In the period up to 20 months following vaccination, the reduction in deaths among 4-14-day-old infants after a single dose of tetanus-diptheria toxoids was about the same as that after two doses. However, beyond 20 months a single dose did not appear to provide protection.

Adolescent↗
PubMed1993

Can Haemophilus influenzae type b-tetanus toxoid conjugate vaccine be combined with diphtheria toxoid-pertussis vaccine-tetanus toxoid?

OBJECTIVE: To assess the side effects and immune responses after three serial doses of PRP-T vaccine (a Haemophilus influenzae type b [Hib]-tetanus toxoid conjugate vaccine) given concurrently or mixed with adsorbed DPT vaccine (diphtheria toxoid-pertussis vaccine-tetanus toxoid). DESIGN: Multicentre randomized controlled trial. SETTING: Four public health units in western Canada. PARTICIPANTS: Healthy infants 8 to 15 weeks old at entry who were able to receive routine primary vaccinations. Of 444 infants enrolled, 433 (98%) completed the study. INTERVENTIONS: All infants received PRP-T and DPT vaccines at 2, 4 and 6 months of age: half received them mixed in one injection and the others as separate, bilateral injections. MAIN OUTCOME MEASURES: Side-effects 24 and 48 hours after each dose and serologic responses to each vaccine component. RESULTS: Follow-up was obtained after all 1312 vaccinations. Fever was infrequent in the two treatment groups. Local adverse effects of the PRP-T vaccine were infrequent and mild (e.g., redness was noted in 5.9% of cases and the area of redness was more than 2.5 cm in diameter in 0.8%). The incidence rate of local effects of the DPT-containing vaccines was the same in the two groups except for tenderness, which was more frequent in the group given the mixed vaccine (26.6% v. 17.9%, p < 0.001). Serologic data were available for 97% of the subjects. After the three doses 98.1% of the subjects had a PRP antibody level of 0.15 micrograms/mL or more, and 87.9% had a level of 1.0 micrograms/mL or more, both levels compatible with protection against Hib. Responses to PRP-T were comparable between the treatment groups as were responses to the diphtheria and tetanus toxoids. Pertussis agglutinin titres were reduced after administration of one of two PRP-T lots mixed with DPT vaccine, but responses to four other pertussis antigens were not impaired. CONCLUSION: PRP-T vaccine is well tolerated and immunogenic. Combined PRP-T and DPT vaccines performed satisfactorily and may be the preferred method of administration.

Antibodies, Bacterial↗
PubMed2000

Ultrastructural localization of the binding fragment of tetanus toxin in putative gamma-aminobutyric acidergic terminals in the intermediolateral cell column: a potential basis for sympathetic dysfunction in generalized tetanus.

Tetanus toxin (TeTx) causes sympathetic hyperactivity, a major cause of mortality in generalized tetanus, apparently by obstructing the inhibition of sympathetic preganglionic neurons (SPNs). Neuroanatomic tracing and immunohistochemistry were used to investigate whether axon terminals in the intermediolateral cell column (IML) that synapse on SPNs and use the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may be infected transsynaptically with TeTx. The binding fragment of TeTx (TTC; an atoxic surrogate of TeTx) and the cholera toxin B subunit (CTB; a retrograde tracer) were injected into the rat superior cervical ganglion and, over 16-48 hours, were transported to the ipsilateral IML in the caudal half of the last cervical and first three thoracic spinal cord segments. With light microscopy, diffuse CTB immunolabeling extended throughout SPN perikarya and dendrites. Punctate TTC and GABA immunolabeling were accumulated densely in the neuropil between and surrounding SPN processes. With electron microscopy, 54% of the axon terminals in the IML (n = 1,337 terminals) were TTC immunolabeled (TTC(+)), and 25% contained putative neurotransmitter levels of GABA immunolabeling (GABA(+)). On average, GABA(+) terminals had a 76% chance of also being TTC(+) and a 62% greater chance of being TTC(+) than GABA(-) terminals (P < 0.000001). Axon terminals were just as likely to be TTC(+) and/or GABA(+) regardless of whether the dendrites they synapsed on were large (>1 microM) or small in cross-sectional area or were labeled retrogradely. Sympathetic hyperactivity in tetanus may involve 1) retrograde and transsynaptic transport of TeTx by SPNs and 2) at least in part, an infection of GABAergic terminals in the IML.

Animals↗
PubMed1995

Botulinum versus tetanus neurotoxins: why is botulinum neurotoxin but not tetanus neurotoxin a food poison?

Botulinum and tetanus neurotoxins, produced by Clostridium botulinum and Clostridium tetani, respectively, are the most poisonous poisons known to mankind. Although botulinum and tetanus neurotoxins share several characteristics, such as similar mol. wts, similar macrostructure, virtually identical mode of action, and a strong amino acid sequence homology, the two neurotoxins differ in one very significant way; only botulinum neurotoxin is a food poison. Factors responsible for the food poisoning potential of botulinum neurotoxins seem to be a group of complexing proteins that are also produced by C. botulinum, and are known to associate with the neurotoxin. Translation products of nucleotide sequences upstream to the neurotoxin genes of serotypes A, B, C, D, E and F botulinum neurotoxin reveal the location of genes for one of the complexing proteins that could be transcribed as polycistronic mRNA to include neurotoxin sequences. No such protein seems to be present in C. tetani, suggesting that the lack of complexing proteins might be responsible for tetanus not being a food poison.

Amino Acid Sequence↗
PubMed1990

Quantitative estimation of diphtheria and tetanus toxoids. 4. Toxoids as international reference materials defining Lf-units for diphtheria and tetanus toxoids.

The Lf-unit, which is used in the control of diphtheria and tetanus toxoid production and in some countries also to follow immunization of horses for production of antitoxins, has hitherto been defined by means of antitoxin preparations. A diphtheria toxoid and a tetanus toxoid preparation, both freeze-dried, were examined in an international collaborative study for their suitability to serve as reference reagents in the flocculation tests and for defining the Lf-units. It was shown that flocculation tests using the reference toxoids are very reproducible and reliable and the WHO Expert Committee on Biological Standardization established: the toxoid called DIFT as the International Reference Reagent of Diphtheria Toxoid for Flocculation Test with a defined content of 900 Lf-units of diphtheria toxoid per ampoule; and the toxoid called TEFT as the International Reference Reagent of Tetanus Toxoid for Flocculation Test with a defined content of 1000 Lf-units of diphtheria toxoid per ampoule.

Animals↗
PubMed1999

Studies on a Hib-tetanus toxoid conjugate vaccine: effects of co-administered tetanus toxoid vaccine, of administration route and of combined administration with an inactivated polio vaccine.

A freeze-dried tetanus toxoid (T) conjugated Haemophilus influenzae type b (Hib) vaccine, was reconstituted in either diphtheria toxoid (D), DT or a combined DT and inactivated polio vaccine (IPV), and administered in an open randomized trial either intramuscularly (i.m. ) or subcutaneously (s.c.) to 287 Swedish infants at three, five and 12 months of age. When not included in the mixture, IPV was administered s.c. at a separate site. The geometric mean concentrations of Hib antibodies after primary and booster vaccinations were 1.0 and 11.6 microg/ml, respectively, with no differences related to co-administration of the carrier protein T. Antibodies against T were induced by the T conjugated Hib vaccine (Hib-T) alone in 69/95 infants aged six months, and in 87/93 children aged 13 months, although infants receiving both Hib-T and T had significantly higher concentrations. Antibody responses to Hib, D, T or polio were not negatively influenced by administration route or by mixing with IPV, except that the mixed vaccine DT-IPV induced lower anti-polio GM titers after primary vaccination than did separate IPV. More local reactions were induced by the s.c. than by the i.m. route (P-values from 0.001 to 0.01). Slight increases in rates of local reactions and febrile events (>/=38 degrees C) occurred by order of dose. The low Hib antibody concentrations after the first two doses in this and other Swedish studies are unlikely to be of clinical relevance. The tetanus antibody response from T as a carrier protein alone was not sufficient for basic tetanus immunization, but should be considered in future use of additional T conjugated vaccines.

Antibodies, Bacterial↗
PubMed2006

Predicting the clinical outcome of tetanus: the tetanus severity score.

OBJECTIVES: To create a new tetanus score and compare it with the Phillips and Dakar scores. METHODS: We used prospectively acquired data from consecutive patients admitted to the Hospital for Tropical Diseases, Ho Chi Minh City, to create the Tetanus Severity Score (TSS) with multivariate logistic regression. We compared the new score with Phillips and Dakar scores by means of resubstituted and prospective data, assessing performance in terms of sensitivity, specificity and area under receiver operator characteristic curves. RESULTS: Resubstitution testing yielded a sensitivity of 77% (298/385) and a specificity of 82% (1,183/1,437) for the TSS; 89% (342/385) and 20% (281/1,437) for the Phillips score; and 13% (49/385) and 98% (1,415/1,437) for the Dakar score. The TSS showed greatest discrimination with 0.89 area under the receiver operator characteristic curve (95% CI 0.88-0.90); this was 0.74 for the Dakar score and (95% CI 0.71-0.77) and 0.66 for the Phillips score (95% CI 0.63-0.70; P values <0.001). Prospective testing showed 65% (13/20) sensitivity and 91% (210/230) specificity for the TSS; 80% (16/20) and 51% (118/230) for the Phillips score; and 25% (5/20) and 96% (221/230) for the Dakar score. The TSS achieved the greatest area under TSS of 0.89 (95% CI 0.82-0.96), significantly greater than the Phillips score [0.74 (0.6-0.88), P = 0.049] but not the Dakar score [0.80, (0.71-0.90), P = 0.090]. CONCLUSIONS: The TSS is the first prospectively developed classification scheme for tetanus and should be adopted to aid clinical triage and management and as a basis for clinical research.

Adolescent↗
PubMed1986

Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen.

We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary.

Antibodies, Bacterial↗
PubMed1987

Differential effects of tetanus toxin on inhibitory and excitatory synaptic transmission in mammalian spinal cord neurons in culture: a presynaptic locus of action for tetanus toxin.

Tetanus toxin reduces monosynaptic inhibitory and excitatory synaptic transmission in mouse spinal cord neurons in culture. Inhibitory transmission is preferentially reduced by the toxin; however, excitatory transmission is also ultimately reduced and blocked by the concentrations of toxin used in these studies. Recordings from monosynaptically connected cell pairs revealed a marked diminution in amplitude of evoked monosynaptic inhibitory postsynaptic potentials coincident with the onset of convulsant action at a time when evoked monosynaptic EPSPs were relatively unaffected. Increased polysynaptic excitation occurred as a result of diminished inhibition. This supports the reduction of inhibition as an important mechanism in the convulsant action of tetanus toxin. Quantal analysis of the late effects of tetanus toxin on the monosynaptic excitatory postsynaptic potential revealed a reduction in quantal number with no reduction in quantal size, thus demonstrating a presynaptic locus of action for the toxin on spinal neurons.

Animals↗
PubMed1989

[A vaccine against tetanus with a higher level of tetanus toxoid].

In an immunological survey of the population it was revealed that the population above 60 years is not adequately protected against tetanus. This is probably to a considerable extent due to changes in the immune system as a result of age-conditioned changes and also due to an inadequate stimulus in the form of vaccine. The author prepared therefore an anti-tetanus vaccine with a higher antigen content. After its administration to a group of elderly subjects experimental evidence was provided of its favourable effect on the formation of tetanic antitoxin. The main attention was focused on the effect of vaccine in prophylaxis of tetanus after injuries.

Aged↗
PubMed1993

Disulfide linkage between C3b and tetanus toxin on tetanus toxin-specific EBV-transformed B cells.

EBV-transformed B cells specific for tetanus toxin were found to bind C3b in excess over the expected figures based on the number of complement receptors CR1. This was confirmed by analysis of cell extracts by SDS-PAGE giving evidence for C3b-membrane protein complexes that were disrupted upon reduction. Alkylation of C3b-free cysteine abolished formation of these complexes and only a noncovalent binding of C3b to CR1 was observed, which could be inhibited by mAb to CR1. When C3b was incubated with the same cells coated with tetanus toxin bound to their specific membrane Ig, preferential formation of disulfide-bonded complexes between tetanus toxin and C3b was observed. These observations correspond to a novel capacity of C3b to interact covalently through its cysteine 1010 with free SH groups of protein acceptors. One hypothesis is that the disulfide bond formation is catalyzed by a thioredoxin-like protein secreted and expressed on the membrane of EBV-transformed B cells. In the context of Ag processing and presentation by B cells, disulfide binding of chaperone C3b to Ag is likely to persist during transcytosis and to play a significant role in the modulation of the processing.

B-Lymphocytes↗
PubMed1998

Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations.

UNLABELLED: With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, > or = 95% of vaccinees had anti-Hib antibody concentrations > or = 0.15 microg/ml and there was a marked booster response (> 100-fold) in all groups. CONCLUSIONS: Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity.

Analysis of Variance↗
PubMed1979

The estimation of the survival rate of tetanus-intoxicated mice. A model for screening anti-tetanus drugs.

The estimation of the survival rate of tetanus-intoxicated mice is suggested to be a useful animal model for assaying the anti-tetanus potency of drugs. This model was tested with the four central depressants phenobarbitone, chlorpromazine, diazepam and halothane. In agreement with their clinical value, diazepam appeared to be the most, phenobarbitone the least effective agent.

Animals↗
PubMed1994

Immunogenicity and safety of Haemophilus influenzae type b-tetanus protein conjugate vaccine alone or mixed with diphtheria-tetanus-pertussis vaccine in infants.

Haemophilus capsular polysaccharide-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) vaccines were administered in a single syringe (group 1) or separate syringes (group 2) to 284 infants at 2, 4, and 6 months of age. Group 1 infants had a slightly greater incidence of local reactions. Systemic reactions were similar. The geometric mean titers of polyribosylribitol phosphate (PRP) serum antibody concentrations after the third dose of PRP-T vaccine were 4.8 and 4.3 micrograms/ml for groups 1 and 2, respectively. Antibody responses to DTP antigens were also similar. The immunogenicity and safety of the PRP-T and DTP vaccines are equivalent when the vaccines are administered in separate syringes or the same syringe to infants.

Antibodies, Bacterial↗