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PubMed1992

Characteristics of toxin-neutralization by anti-tetanus human monoclonal antibodies directed against the three functional domains [A], [B] and [C] of the tetanus toxin molecule and a reliable method for evaluating the protective effects of monoclonal antibodies.

Five anti-tetanus human monoclonal antibodies (MAbs) produced by hybrid cell lines we established previously were characterized. Their abilities to neutralize tetanus toxin in vitro and to protect mice against challenge with toxin were studied by observing the changes in the progress of symptoms in mice. Immunostaining showed that MAbs MAb-G4 and G2 recognized the N-terminal domain, [A] and the C-terminal domain, [C] of the tetanus toxin molecule, respectively, while MAbs MAb-G1, G3 and G6 recognized its middle domain, [B]. Enzyme-linked immunosorbent assay showed that the binding affinity of MAb-G3 was 2.9 x 10(10) M-1 and those of the other MAbs were as high as approximately 10(11) M-1. In in vitro neutralization experiments, at sufficient doses all the MAbs as single reagents protected mice completely against the effect of tetanus toxin. However, at lower doses than those sufficient to rescue mice, the kinetic patterns of progress of symptoms with the individual MAbs differed with each other and, except for MAb-G4, were different from that of anti-tetanus human polyclonal antibody. They suppressed the development and/or slowed the rate of progress of symptoms for over 96 h and delayed death of the mice. We propose that the comparison of the minimum survival dose with that of human polyclonal antibody of known international units is a reliable method for estimating the actual protective activity of a MAb. Intravenous (IV) injection of doses of individual MAbs or their mixtures at over 0.03 IU per mouse protected mice from subsequent challenge with 20 MLD of tetanus toxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Tetanus immunity after diphtheria, tetanus toxoids, and acellular pertussis vaccination in children with clinically stable HIV infection.

BACKGROUND: HIV infection often impairs the immune response to childhood vaccines. OBJECTIVE: We sought to study the ability of HIV-infected children receiving highly active antiretroviral therapy (HAART) to generate a booster response to immunization with a recall antigen to which they had lost humoral immunity. METHODS: Diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccination was given at either 16 or 36 weeks after initiation of HAART to 37 HIV-infected children 2 to 9 years of age with a history of DTaP or diphtheria-tetanus-pertussis receipt who had negative tetanus antibody titers (<or=1:243) at baseline. RESULTS: There was a clear increase in tetanus titers after vaccination, with an increase of 27-fold over the baseline values at weeks 4 and 8. The effect on tetanus titers faded to a 9-fold and 3-fold increase over baseline values at weeks 18 and 32, respectively. DTaP vaccination did not affect HIV-1 RNA viral load or CD4 percentage or cell count. There was no increase in either acute or long-term adverse events associated with the DTaP vaccination. CONCLUSION: Although children with stable HIV infection receiving HAART can mount antigen-specific responses to tetanus immunization, the durability of these responses might be limited. Long-term monitoring of specific immune function in such children is indicated.

Animals↗
PubMed1987

Antibacterial immunity and its modeling in experimental tumor tetanus and wound tetanus of the mouse.

The experimental and theoretical analysis of the tumor-tetanus phenomenon has provided us with new insights into the pathogenesis of tetanus infection. Our theoretical model of clostridial propagation in the proliferating tissue is based upon the principle of mitosis-controlled rod division (hit and cloning model). It has lent itself to the description of early growth stages of the clostridial rod population in our experiments of tumor tetanus and of wound tetanus of the mouse. However, the later course of the tetanus lethality curves under antitoxin protection, about a week following injection of the tumor cell-spore or CaCl2-spore suspensions, reveals a pronounced delay in clostridial propagation. Based on our model we can explain this process by a humoral immune reaction directed against the clostridial rods taking into account the variability of elimination of the heterologous tetanus antitoxin applied. The experimental results are in good agreement with those obtained by computer simulation. The theoretical knowledge resulting from these studies can be used for the interpretation of the serodiagnostic tumor test with apathogenic clostridia as well as for the quantitative assessment of the malignancy of neoplastic growth.

Animals↗
PubMedDate not supplied

A randomized double-blind sham-controlled study of intrathecal human anti-tetanus immunoglobulin in the management of tetanus.

BACKGROUND: Tetanus is a major cause of mortality and morbidity in developing countries. Various modalities of treatment to prevent progression of the disease and alter its outcome have been tried. This study was designed to evaluate the role of intrathecal human anti-tetanus immunoglobulin (TIG) in the management of tetanus. METHODS: Thirty-six adult patients presenting to an university-affiliated teaching hospital were stratified based on the severity of disease into mild and severe disease, and subsequently randomly allocated to receive either 250 i.u. of TIG intrathecally or a sham procedure mimicking the lumbar puncture. RESULTS: In mild tetanus, TIG administration significantly retarded the rate of progression (p = 0.05), reduced the duration of hospital (p = 0.01) and intensive care unit stay (p = 0.05), need for tracheostomies (p = 0.03) and the dose of sedatives required for control of spasms (p = 0.01). In mild tetanus, the mortality rates were 20% and 30% in the treated and control groups, respectively. CONCLUSION: We suggest that TIG is useful in reducing the morbidity, progression of disease and mortality in patients presenting with mild tetanus.

Adult↗
PubMed2006

Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel.

On June 10, 2005, a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) formulated for use in adults and adolescents was licensed in the United States for persons aged 11-64 years (ADACEL, manufactured by sanofi pasteur, Toronto, Ontario, Canada). Prelicensure studies demonstrated safety and efficacy, inferred through immunogenicity, against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adults. To reduce pertussis morbidity among adults and maintain the standard of care for tetanus and diphtheria prevention and to reduce the transmission of pertussis to infants and in health-care settings, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adults aged 19-64 years should receive a single dose of Tdap to replace tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they received their last dose of Td >or=10 years earlier and they have not previously received Tdap; 2) intervals shorter than 10 years since the last Td may be used for booster protection against pertussis; 3) adults who have or who anticipate having close contact with an infant aged <12 months (e.g., parents, grandparents aged <65 years, child-care providers, and health-care personnel) should receive a single dose of Tdap to reduce the risk for transmitting pertussis. An interval as short as 2 years from the last Td is suggested; shorter intervals can be used. When possible, women should receive Tdap before becoming pregnant. Women who have not previously received Tdap should receive a dose of Tdap in the immediate postpartum period; 4) health-care personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap. An interval as short as 2 years from the last dose of Td is recommended; shorter intervals may be used. These recommendations for use of Tdap in health-care personnel are supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC). This statement 1) reviews pertussis, tetanus and diphtheria vaccination policy in the United States; 2) describes the clinical features and epidemiology of pertussis among adults; 3) summarizes the immunogenicity, efficacy, and safety data of Tdap; and 4) presents recommendations for the use of Tdap among adults aged 19-64 years.

Adult↗
PubMed1991

Impact of a tetanus toxoid immunization mass campaign on neonatal tetanus mortality in Aceh Province, Indonesia.

Neonatal tetanus mortality declined dramatically in Pidie district (Aceh Province) Indonesia between 1984 and 1987. Baseline and follow-up survey results demonstrated an 85% reduction in neonatal tetanus mortality during this period, from 32.1/1000 live births to 4.9/1000 live births. During 1985 a tetanus toxoid mass campaign was conducted in Pidie district which resulted in 84% of women 10-45 years of age receiving two tetanus toxoid injections. Analysis of the results of the two surveys provides very strong evidence of the impact of the tetanus toxoid mass campaign on neonatal tetanus mortality.

Adolescent↗
PubMed1976

Active immunization against tetanus in guinea-pigs. An attempt to evaluate "rapid immunization" with tetanus vaccine.

The effect of 3 schedules for tetanus vaccination on the immunity developed by guinea-pigs was investigated, using 1.5 Lf adsorbed tetanus toxoid injected subcutaneously. The following injection schedules were used: a) 5 injections: initially and after 3, 7, 10, and 13 days; b) 3 injections:: initially and after 2 and 4 weeks; c) 2 injections: initially and after 4 weeks. Blood samples were taken after 1, 2, 3, 4, 6, and 8 weeks and the titres of tetanus antitoxin were recorded. No significant difference in the titres was observed within 2 weeks. Immunity was also tested by challenge with different amounts of tetanus toxin after 1 week, 10 days, 2, 3, and 8 weeks. A tendency to a higher immunity with schedule a) was observed after 10 days to 2 weeks; thereafter no acceleration of immunity could be shown. The results indicate that frequent injections over a short period of time do not establish rapid immunity against tetanus.

Animals↗
PubMed1987

The role of cell population kinetics in the efficacy of penicillin--an experimental analysis and stochastic modeling of the tumour tetanus and wound tetanus of the mouse.

When investigating tetanus lethality summation curves of mice under comparable quantitative conditions following a temporarily limited administration of penicillin, the curves obtained can be calculated by the kinetics of tumour cells or wound fibroblasts. In particular, it has been shown that the optimal efficacy of penicillin, after short-time usage as compared with a long-time administration schedule, is determined by the generation time of the tetanus rods as a function of the mitotic cycle of the "pace-making" tumour cells or wound fibroblasts. Further variables of the mathematical model imply the pharmacokinetics of penicillin and the recovery process of the "hit" tetanus rods. From these results some basic experimental and clinical tetanus issues can be elucidated; thus, the mitosis theory of tetanus is being verified for the stage of incubation and of clinical manifestation, while the classical necrosis theory of the pathogenesis of tetanus infection should be valid only for the final stage.

Animals↗
PubMed2001

Tetanus antibody levels of female volunteers after injection with solvent/detergent-treated human tetanus immunoglobulin (Tetabulin S/D).

BACKGROUND AND OBJECTIVES: The aim of this study was to analyse the increase of antitetanus titre in volunteers following injection with human tetanus immunoglobulin (HTI). MATERIALS AND METHODS: Twelve females with tetanus antibody titres of < or = 0.05 international units (IU)/ml were injected with 500 IU of human tetanus immunoglobulin (Tetabulin S/D). The tetanus antibody titres were determined before injection, and after 30 h, 48 h and 4 days. RESULTS: A fast and sustained increase of protective tetanus antibody levels was observed in 10 of 12 volunteers. No adverse events related to the study drug were reported. CONCLUSIONS: HTI confers rapid and effective immunity to tetanus.

Aged↗
PubMed2000

Effects of diphtheria-tetanus-pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States.

BACKGROUND: Findings from animal and human studies confirm that diphtheria and tetanus toxoids and pertussis (DTP) and tetanus vaccinations induce allergic responses; associations between childhood vaccinations and subsequent allergies have been reported recently. OBJECTIVE: The association of DTP or tetanus vaccination with allergies and allergy-related respiratory symptoms among children and adolescents in the United States was assessed. METHODS: Data were used from the Third National Health and Nutrition Examination Survey on infants aged 2 months through adolescents aged 16 years. DTP or tetanus vaccination, lifetime allergy history, and allergy symptoms in the past 12 months were based on parental or guardian recall. Logistic regression modeling was performed to estimate the effects of DTP or tetanus vaccination on each allergy. RESULTS: The odds of having a history of asthma was twice as great among vaccinated subjects than among unvaccinated subjects (adjusted odds ratio, 2.00; 95% confidence interval, 0.59 to 6.74). The odds of having had any allergy-related respiratory symptom in the past 12 months was 63% greater among vaccinated subjects than unvaccinated subjects (adjusted odds ratio, 1.63; 95% confidence interval, 1.05 to 2.54). The associations between vaccination and subsequent allergies and symptoms were greatest among children aged 5 through 10 years. CONCLUSIONS: DTP or tetanus vaccination appears to increase the risk of allergies and related respiratory symptoms in children and adolescents. Although it is unlikely that these results are entirely because of any sources of bias, the small number of unvaccinated subjects and the study design limit our ability to make firm causal inferences about the true magnitude of effect.

Adolescent↗
PubMed1996

Cross reactive anti-tetanus and anti-melittin Fab fragments by phage display after tetanus toxoid immunisation.

Amino acid sequence homology between tetanus toxoid, a common vaccine and melittin, a bee venom allergen provided us with two antigen models for studying the production of cross reactive antibodies after immunisation. Analysis of the serum of an atopic patient recently boosted with tetanus toxoid revealed the presence of anti-melittin and anti-tetanus antibodies. From this donor a phage display Fab library was constructed five days after vaccination. Screening of this library either with melittin alone or with tetanus toxoid followed by melittin allowed the isolation of Fab fragments specific to melittin but also Fab fragments which cross react with melittin and tetanus toxoid. Amino acid analysis revealed diversity in the heavy and the light Ig chains of the melittin specific and of the cross reactive clones. Interestingly we found that the light chain recognised melittin whereas the heavy chain preferentially bound to tetanus toxoid suggesting that cross reactivity may be due to the different binding specificities of the individual Ig chains.

Amino Acid Sequence↗
PubMed2003

Seroprevalence of tetanus antibody in Turkish population and effectiveness of single-dose tetanus toxoid.

The study presented here was performed to determine the rates of immunity to tetanus in a cross section of the Turkish population and to assess the impact of a single-dose tetanus toxoid in previously unvaccinated individuals. Among 18-year-old participants who received their last tetanus booster 4 years prior to the study and 22-year-old participants who received the booster 8 years previously, certain durable protective antibody (>1 IU/ml) was detected in 100%. However, only 3.3% of 20-year-old participants who did not know whether they had been vaccinated as children or young adults had a protective antibody level. After administering a single dose of tetanus vaccine to this group, the rate of protective antibody increased from 3.3% to 96.7%. For the prevention of tetanus, the optimal policy should focus on improving rates of complete primary immunization in adults and children and giving a single booster every 10 years, or at least at age 40 or 50 years.

Adolescent↗
PubMed2005

Attenuated immune response to tetanus toxoid in young healthy men protected against tetanus.

Tetanus booster is a routine procedure of tetanus prevention in populations with high risk of injury, independent of the levels of protection. But the immune response in already protected individuals is not well studied. We describe the kinetics of booster response in individuals by measuring tetanus antitoxin levels by indirect ELISA. A 6-month follow up was performed on 60 boosted individuals tested before, 1 week, 1, 2, 3 and 6 months after the booster. High initial protection (mean titer 1.08 IU/ml) and less than 3-fold increase after 1 month were observed. After 1 month of stable antitoxin levels, the levels slowly decreased and reached a mean titer of 1.78 IU/ml after 6 months. Individuals with initial levels <1 IU/ml had booster response after the first month twice as high compared to those with initial level >or=1 IU/ml. However, in both groups, the decline from 1 to 6 months was about 2-fold. Individuals already protected against tetanus exhibited an attenuated, short-lasting booster response to tetanus toxoid. This was more pronounced in individuals with pre-booster levels >or=1 IU/ml, who did not improve immune protection after the booster.

Adolescent↗
PubMed1989

[Oral immunization against tetanus, using liposome-entrapped tetanus toxoid].

A study was made on oral immunization using a tetanus toxoid. Liposome entrapped tetanus toxoid (LTT) was p.o. administered to cats and serum antibody responses were examined. As a result it was known that the LTT antigen induced antibody production in the serum and that an antitoxin antibody titer higher than 0.1 IU/ml, a prophylactic level against tetanus, was produced. On the contrary to this, no antibody was detected in the group administered a tetanus toxoid alone throughout the test period. Also, when an absorbed tetanus toxoid (ATT) was booster-injected to cats p.o. primed with LTT, high responses of the secondary immunization were obtained. Moreover, in case LTT was p.o. administered as a booster antigen, the antitoxin titer in the serum showed a rapid, steep elevation. From these results it has been clarified that LTT on p.o. administration produces an antibody equivalent to the subcutaneous inoculation of ATT.

Administration, Oral↗
PubMed1994

Neutralizing antibodies and immunoprotection against pertussis and tetanus obtained by use of a recombinant pertussis toxin-tetanus toxin fusion protein.

The currently available diphtheria-tetanus-whole-cell pertussis (DTP) vaccines are associated with a variety of problems, including undesirable side effects and inconsistent efficacy. These problems are probably related to the poor definition of such vaccines, especially with respect to the whole-cell component against pertussis. Ideal vaccines should include only immunoprotective antigens with no toxin activity. As an initial step towards obtaining a well-defined and simplified DTP vaccine, a pertussis toxin-tetanus toxin chimeric protein was constructed. A soluble form of the pertussis toxin S1 subunit was fused to the protective fragment C of tetanus toxin, and the recombinant hybrid protein was produced in Escherichia coli. The 75-kDa fusion protein (p75) was overexpressed as a soluble molecule and purified to near homogeneity by two consecutive chromatographic steps. Purified p75 retained its ability to bind to ganglioside GT1b, the receptor for tetanus toxin, and to be recognized by protective and neutralizing anti-pertussis toxin antibodies specific for conformational epitopes. When administered to mice, the hybrid protein was found to be nontoxic but immunogenic. In addition, it was capable of inducing strong protection against tetanus and some protection against pertussis, as well as eliciting a pertussis toxin-neutralizing antibody response. Although the levels of anti-pertussis toxin antibodies were rather low, neutralizing titers of the immunized mice correlated well with anti-pertussis toxin titers, indicating that protective epitopes are conserved in the recombinant protein.

Animals↗
PubMed1997

Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems.

An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989 WHO adopted the goal of eliminating NT as a public health problem worldwide. To achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that newborns be passively protected at birth by the antepartum administration of at least two doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP) vaccine. For this strategy to be effective, the TT used must be immunogenic. Potential factors that may affect TT immunogenicity need to be evaluated if NT is to be eliminated and if non-NT is to be controlled. Although data are conflicting, concurrent malarial infection may decrease the immune response to TT; however, malarial chemoprophylaxis may enhance the immune response. Malnutrition does not appear to affect immunogenicity; nevertheless, one study suggests that vitamin A deficiency is associated with an impaired immune response. Although it has been postulated that placental transfer of tetanus antibody is impaired in African women, a survey of the published literature suggests that this is not the case. Freezing TT has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation.

Adult↗
PubMed2006

Tactile fade detection with hand or wrist stimulation using train-of-four, double-burst stimulation, 50-hertz tetanus, 100-hertz tetanus, and acceleromyography.

Residual neuromuscular blockade can be evaluated using acceleromyography, tactile assessment of train-of-four (TOF), double-burst stimulation (DBS), 50-Hz tetanus, or 100-Hz tetanus. Nerve stimulation can be at the hand or the wrist. We compared all these tests at both sites of stimulation. Rocuronium was given to 32 patients under sevoflurane anesthesia. The mechanomyographic adductor pollicis TOF ratio was measured at one extremity. In the other, stimulation was at the hand or the wrist, by random allocation, and the acceleromyographic TOF ratio was measured. During recovery, a blinded observer estimated tactile fade. The TOF fade became undetectable when mechanomyographic TOF ratio was (mean +/- sd) 0.31 +/- 0.15. For DBS, this threshold was 0.76 +/- 0.11. For 50-Hz tetanus, it was 0.31 +/- 0.15. For 100-Hz tetanus, it was 0.88 +/- 0.18, with a range of 0.14-1.00. These tactile responses were the same for hand and wrist stimulation. When acceleromyographic TOF ratio reached 1.0, the mechanomyographic TOF ratio was 0.89 +/- 0.06. With stimulation in the hand, acceleromyographic TOF ratio >1.0 was less frequent than at the wrist. To exclude residual paralysis, TOF, DBS, and 50-Hz tetanus are inadequate, 100-Hz tetanus is unreliable, and acceleromyography performs best.

Adult↗