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PubMed2004

Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine.

Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant capable of enhancing host immune responses specific to unrelated, mucosally co-administered vaccine antigens. When mice were administered intranasally with diphtheria-pertussis-tetanus (DPT) combination vaccine consisting of diphtheria toxoid (DTd), tetanus toxoid (TTd), pertussis toxoid (PTd), and formalin-treated filamentous hemagglutinin (fFHA), the presence of rCTB elevated constantly high values of DTd- and TTd-specific serum ELISA IgG antibody titres, and protective levels of diphtheria and tetanus toxin-neutralizing antibodies but the absence of rCTB did not. Moreover, the addition of rCTB protected all mice against tetanic symptoms and deaths. DPT combination vaccine raised high levels of serum anti-PT IgG antibody titres regardless of rCTB and protected mice from Bordetella pertussis challenge. These results suggest that co-administration of rCTB as an adjuvant is necessary for induction of diphtheria and tetanus antitoxin antibodies on the occasion of intranasal administration of DPT combination vaccine.

Adjuvants, Immunologic↗
PubMed2001

Tetanus immunization in pregnant women: evaluation of maternal tetanus vaccination status and factors affecting rate of vaccination coverage.

The objectives of this study were to determine the tetanus vaccination status for pregnant women, and to examine the effects of various factors on tetanus toxoid (TT) vaccination coverage during pregnancy in reproductive-age women. Four-hundred and ninety-three postpartum women who had live births at a hospital in Ankara were interviewed and information was collected on the mothers' sociodemographic characteristics, TT vaccination history, and prenatal care during the pregnancy studied. The rates for no vaccination, one-dose vaccination, and two-dose vaccination were 53.3%, 18.9%, and 27.8%, respectively. The vaccinated women (with at least one dose) were significantly younger, of lower parity, and had attended more prenatal care visits than the unvaccinated women. Of the women who attended at least one prenatal care check-up, only about half were vaccinated. Significantly more rural women were vaccinated against tetanus than urban women. Current vaccination rates with TT during pregnancy were found to be well below universal levels. Turkey needs to launch effective mass media campaigns that target urban and suburban populations, and inform and motivate women to request vaccination against tetanus.

Adult↗
PubMed1997

Lymphocyte response to tetanus toxoid among Indonesian men immunized with tetanus-diphtheria during extended chloroquine or primaquine prophylaxis.

Immune suppression, a potential side effect of long-term chemoprophylaxis, was evaluated as part of a randomized, placebo-controlled trial that compared daily primaquine against weekly chloroquine for malaria prevention. In the last month of the year-long trial, baseline in vitro lymphoproliferative responses to tetanus toxoid were measured, and a tetanus-diphtheria (Td) immunization was administered. Proliferative responses to tetanus toxoid in each Td-immunized group increased significantly over pre-Td baselines and those of the unvaccinated control. Highest initial responses were measured in the primaquine group. The proportion of responders and the magnitude of proliferation was consistently low in the chloroquine group, and end point responses in this group were significantly below those of the placebo. These results suggest that the development and duration of the cellular response to tetanus immunization was impaired by long-term weekly chloroquine prophylaxis, while daily primaquine prophylaxis over the same time period had no inhibitory effect.

Adult↗
PubMed1997

Vaccine antigen interactions after a combination diphtheria-tetanus toxoid-acellular pertussis/purified capsular polysaccharide of Haemophilus influenzae type b-tetanus toxoid vaccine in two-, four- and six-month-old infants.

OBJECTIVE: The safety and immunogenicity of a diphtheria-tetanus toxoid-acellular pertussis vaccine (DTaP; Trepedia)/Haemophilus influenzae b polysaccharide (PRP-T; ActHib) combined vaccine (TriHibir; Pasteur Mérieux Connaught) was compared with DTaP and PRP-T given at the same visit but at separate sites in a prospective multicenter, open label trial. METHODS: Infants were randomized to four groups (three consistency lots of DTaP/PRP-T vs. one of the consistency lots given as separate vaccines); injections were administered at 2, 4 and 6 months of age. Pre-Dose 1 and post-Dose 3 sera were assayed for antibody titers against all antigens. Reactions to the vaccinations were assessed by parent questionnaire for 30 days after each injection visit. RESULTS: Four hundred eighty-five infants were enrolled; 296 evaluable infants were included in the DTaP/PRP-T group compared with 70 infants in the DTaP and PRP-T vaccine group. Infants who received the combined vaccine had higher post-Dose 3 geometric mean antibody titers to diphtheria antitoxin (P < 0.01) and pertussis filamentous hemagglutinin (P < 0.05) and lower geometric mean antibody titers to tetanus antitoxin (P < 0.05) and Haemophilus influenzae b (Hib) polysaccharide (PRP) (P < 0.05). The geometric mean anti-PRP antibody titer in the DTaP/PRP-T group was 4.3 micrograms/ml compared with 7.0 micrograms/ml in the separate vaccine group (P < 0.05), and the percentage of infants with antibody titers > or = 0.15 and 1 microgram/ml were, respectively, 95 and 86%, whereas they were 100% for both titers in the separate vaccines group. DTaP/ PRP-T vaccine given concomitantly or 1 month apart from hepatitis B vaccine and oral poliomyelitis vaccine caused no significant differences in immunogenicity or safety. The safety assessments for the DTaP/PRP-T vaccine showed no consistent differences in systemic or local injection site reactions compared with DTaP and PRP-T administered separately. CONCLUSION: Although the antibody responses to tetanus and Hib polysaccharide in the evaluated DTaP/PRP-T combined vaccine were significantly lower than those seen after separate DTaP and PRP-T administration, the combined vaccine elicited an immune response against diphtheria, tetanus, pertussis and Haemophilus influenzae b likely to confer protection.

Analysis of Variance↗
PubMed2004

Sm14 of Schistosoma mansoni in fusion with tetanus toxin fragment C induces immunoprotection against tetanus and schistosomiasis in mice.

We have constructed vectors that permit the expression in Escherichia coli of Schistosoma mansoni fatty acid-binding protein 14 (Sm14) in fusion with the nontoxic, but highly immunogenic, tetanus toxin fragment C (TTFC). The recombinant six-His-tagged proteins were purified by nickel affinity chromatography and used in immunization and challenge assays. Animals inoculated with TTFC in fusion with or coadministered with Sm14 showed high levels of tetanus toxin antibodies, while animals inoculated with Sm14 in fusion with or coadministered with TTFC showed high levels of Sm14 antibodies. In both cases, there were no changes in the type of immune response (Th2) obtained with the fusion proteins compared to those obtained with the nonfused proteins. Mice immunized with the recombinant proteins (TTFC in fusion with or coadministered with Sm14) survived the challenge with tetanus toxin and did not show any symptoms of the disease. Control animals inoculated with either phosphate-buffered saline (PBS) or Sm14 died with severe symptoms of tetanus after 24 h. Mice immunized with the recombinant proteins (Sm14 in fusion with or coadministered with TTFC) showed a 50% reduction in worm burden when they were challenged with S. mansoni cercariae, while control animals inoculated with either PBS or TTFC were not protected. The results show that the expression of other antigens in fusion at the carboxy terminus of TTFC is feasible for the development of a multivalent recombinant vaccine.

Animals↗
PubMed1989

Role of intrathecal tetanus antitoxin (equine) in tetanus neonatorum.

The present study includes 50 cases of tetanus neonatorum who were given 200 IU of tetanus antitoxin (equine) intrathecally once only and 500 IU intravenously daily for 3 consecutive days. Nutrition was provided with intravenous drip containing dextrose and other electrolytes. The overall mortality was 78%. It appears that the course of the disease remains unaltered with intrathecal tetanus antitoxin in tetanus neonatorum.

Humans↗
PubMed1998

[Anti-tetanus vaccination after 3 cases of tetanus in a basic rural health area].

OBJECTIVES: a) To find the prevalence of anti-tetanus vaccination in a health district, and b) to detect difficulties in the implementation of corrective measures, after the appearance of three cases of tetanus in 6 months. DESIGN: An observational descriptive crossover study. SETTING: Primary care. Rural health district with 18266 inhabitants. PARTICIPANTS: People of both sexes over 14 from the 3 population nuclei, which had the best records of attendance and vaccination in the health district. INTERVENTIONS: Vaccination coverage at the start and end of the intervention for 328 people chosen by systematic randomised sampling. SOURCE OF DATA: clinical records. MAIN MEASUREMENTS AND RESULTS: At the start of the intervention there was less vaccination coverage among males, over-50s and people living in small nuclei of population. During the study period vaccination coverage increased more in the nuclei where there had been a tetanus case. Vaccines were lacking at the start of the intervention. CONCLUSIONS: A low use of clinical records in the health district was detected, which posed difficulties for the research. Except for one of the population nuclei, very few people at the start of the study were recorded as correctly vaccinated. It is seen that the health service responded slowly to such serious cases as these. It is suggested that primary health care activities should be programmed more in accord with the health problems prevailing in each area. With an illness like tetanus we should not wait for a case to occur before acting.

Catchment Area, Health↗
PubMed1995

Does tetanus immune globulin interfere with the immune response to simultaneous administration of tetanus-diphtheria vaccine? A comparative clinical trial in adults.

In the management of wounds, sometimes it is recommended to give an adult-type tetanus-diphtheria (Td) vaccine dose plus tetanus immune globulin (TIG). Sixty and 59 healthy young adults previously immunized against tetanus (T) and diphtheria (D) were randomized to receive intramuscularly either Td vaccine alone (group 1) or Td vaccine plus 500 IU of TIG (group 2) simultaneously. Antitoxin response was assessed after 4 weeks and 4 months. Circulating antibodies were measured by enzyme-linked immunosorbent assay (ELISA). The cutoff of these tests was 0.1 IU/mL. Titers of 0.1 IU/mL or greater were considered protective. For geometric mean titers (GMT), antibody titers below the cutoff of the assay were given, arbitrarily, 0.05 IU/mL. At 4 weeks, 98% or more of the subjects in group 1 had circulating T and D antitoxin levels of 0.1 IU/mL or higher; in group 2, 95% and 90% of the subjects had titers above this limit for T and D, respectively. At 4 months, these percentages were 98% and 95% for T antitoxin levels in groups 1 and 2, respectively; whereas 96% and 88% of the subjects in groups 1 and 2 had D antitoxin levels of 0.1 IU/mL or higher, respectively. Significantly (P < .05) higher GMTs were seen at the 4-week assessment (but not at 4 months) in group 1, as compared with group 2, in both T and D antitoxin levels (9.91 IU/mL versus 5.60 IU/mL for T antitoxin, and 2.86 IU/mL versus 1.45 IU/mL for D antitoxin). This finding resulted from those participants with low (< 0.1 IU/mL) prevaccination antibody titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

IgG1 is the predominant subclass of in vivo- and in vitro- produced anti-tetanus toxoid antibodies and also serves as the membrane IgG molecule for delivering inhibitory signals to anti-tetanus toxoid antibody-producing B cells.

Peripheral blood leukocytes from individuals immunized with tetanus toxoid can be stimulated by pokeweed mitogen to produce IgG anti-tetanus toxoid antibody (IgG-Tet) in vitro. Previous studies have shown that treatment of these cells with tetanus toxoid or anti-human IgG reagents can inhibit this in vitro antibody synthesis. We have examined the four IgG subclasses on the surface of B cells for their relative contributions in the anti-IgG antibody-induced inhibition of IgG-Tet production. With all donors, the inclusion of anti-IgG1, but not anti-IgG2, -IgG3, or -IgG4, antiserum resulted in the in vitro inhibition of IgG-Tet synthesis. The magnitude of this inhibition was similar to that induced by treatment of the B cells with tetanus toxoid antigen. When the supernatants from normal in vitro cultures were assayed for IgG-Tet of the various IgG subclasses, it was observed that the IgG-Tet were almost exclusively IgG1. Similar results were obtained when serum IgG-Tet were measured. Thus, IgG1 appears to be the major subclass for (1) the in vivo-produced IgG-Tet, (2) the in vitro-produced IgG-Tet, and (3) the membrane receptor which can selectively convey an inhibitory signal to the IgG-Tet B cell.

Antibody Formation↗
PubMed1991

Tetanus toxin receptor. Specific cross-linking of tetanus toxin to a protein of NGF-differentiated PC 12 cells.

A subclone of rat pheochromocytoma cells expresses high affinity receptors for tetanus toxin on differentiation with NGF [Walton, K.M., Sandberg, K., Rogers, T.B. and Schnaar, R.L. (1988) J. Biol. Chem. 263, 2055-2063]. In the presence of protein cross-linking agents, [125I]tetanus toxin, bound to these cells at 0 degree C, forms a cross-linked product with apparent molecular weight of 120 kDa. The formation of [125I]tetanus toxin conjugate involves the heavy chain of the toxin, is prevented by cold toxin and it is largely reduced by pretreating cells with proteases. The cross-linked product is formed only upon incubation of the toxin with NGF-differentiated cells. These results suggest that a protein with apparent molecular weight of 20 kDa is involved in the neurospecific binding of tetanus toxin.

Animals↗
PubMed1999

Reactogenicity and immunogenicity of reduced antigen content diphtheria-tetanus-acellular pertussis vaccines as a booster in 4-7-year-old children primed with diphtheria-tetanus-whole cell pertussis vaccine before 2 years of age.

BACKGROUND: The recent introduction of acellular pertussis vaccines (Pa) offers the possibility of booster doses in older children and adults. This can be conveniently accomplished by combining acellular pertussis antigens with diphtheria and tetanus toxoids. However the optimal dosage for the booster injection has not yet been determined. OBJECTIVE: To compare the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis vaccines (DTPa) with lower antigen contents to a licensed DTPa vaccine when given at 4-7 years of age as a booster to DTPw-primed children. METHODS: Two hundred and twenty-six children primed with four doses of DTPw before 2 years of age were enrolled and allocated to three groups to receive one dose of either DTPa (Infanrix, SmithKline Beecham, Biologicals), a reduced antigen formulation of this vaccine (dtpa, SmithKline Beecham Biologicals), or an experimental low dose formulation (dtpa-exp; d and t, Michigan Biologic Products Institute). Reactogenicity was assessed using diary cards for 15 days. Immunogenicity was determined as antibody responses against the vaccine components in pre- and 1 month postvaccination sera. RESULTS: Of the 225 children who completed the study, 60.0-66.7% reported symptoms, with no significant differences in rates between groups. Local, systemic and unsolicited symptoms occurred with similar frequencies in all three groups, the vast majority (> 90%) being considered as mild or moderate. No serious adverse events related to vaccination were reported. After vaccination, all subjects displayed seroprotective concentrations against diphtheria and tetanus, and 98.7-100% had antibodies against the three pertussis component antigens. The group receiving the reduced dose of the licensed vaccine showed antibody concentrations comparable to those of the full dose group. However, the group receiving the experimental low dose formulation had statistically significantly lower antibody concentrations against both diphtheria and tetanus toxoids compared with the two other groups, as well as significantly lower anti FHA antibody concentrations. CONCLUSIONS: Reducing the antigen content of dtpa had no deleterious effect on the immunogenicity of the vaccine when given as a fifth dose at 4-7 years of age in DTPw-primed children. The reactogenicity profile of both the reduced antigen dtpa vaccines and DTPa were acceptable, the vast majority of local and systemic reactions being considered as mild to moderate, with no vaccine-related serious adverse events reported. The use of lower antigen content dtpa vaccine as a booster in children aged 4-7 is safe and immunogenic.

Antibodies, Bacterial↗
PubMed1982

A comparative clinical study of Adsorbed Tetanus Vaccine and Adult-type Tetanus-Diphtheria Vaccine.

A limited assessment of immunity to diphtheria revealed that only 44.8% of adults had protective levels (greater than 0.01 U/ml) of diphtheria antitoxin in their sera. In the light of this information, it was decided to assess the suitability of Adult-type Tetanus-Diphtheria Vaccine as a replacement for Adsorbed Tetanus Vaccine in occupational health schemes. A comparative study of these vaccines showed that a single dose of each produced an equivalent rate and level of tetanus antitoxin responses. Adult-type Td Vaccine elicited more than fourfold increases of diphtheria antitoxin in 76% of vaccinees. No statistically significant differences were observed in the clinical reactivity of the vaccines under test. However, the combined vaccine caused a slightly higher incidence of local reactions (pain, redness and swelling) while recipients of Adsorbed Tetanus Vaccine more frequently experienced pain.

Adolescent↗
PubMed1993

Neutralization of tetanus toxin by human monoclonal antibodies directed against tetanus toxin fragment C.

Two hybridomas (designated 143 and 147) producing human monoclonal antibodies (IgG1) directed against tetanus toxin were established by fusion of Epstein-Barr virus transformed human peripheral B lymphocytes with the heteromyeloma SPAM-8. The hybridomas produced antibodies in concentrations of approx. 3.5 micrograms/ml (hybridoma 143) and 6.4 micrograms/ml (hybridoma 147) using conventional flask cultures and 33.9 micrograms/ml and 36.2 micrograms/ml, respectively, in dialysis cultures. The antibodies were shown to react with tetanus toxin, toxoid and fragment C in ELISA, and reactivity with tetanus toxin and fragment C was confirmed in SDS-polyacrylamide gel electrophoresis followed by Western blots. The antibody binding sites were located to two different epitopes of fragment C as shown in a competition assay using biotinylated antibodies. Furthermore, binding of both antibodies to fragment C was inhibited by the addition of the receptor-associated ganglioside GT1b. Neutralization of tetanus toxin in concentrations equivalent to 100-120 IU per mg of antibody was observed for both antibodies in a mouse protection assay.

Antibodies, Monoclonal↗
PubMed2004

[Increased level of tetanus antibody twenty one years after a booster dose of tetanus vaccine].

We report the case of a 37 years old woman who asked for clinical advice about revaccination with tetanus toxoid. An adverse reaction to the last booster dose of vaccine, 21 years before, was recorded by a clinical doctor on the vaccination card. It was decided to evaluate serum antibody levels against tetanus and other diseases included in the Portuguese Vaccination Programme. The level of serum tetanus antitoxin (IgG) observed (6.4 IU/ml) corresponds to high protection against the disease and furthermore it is considered as a contraindication to vaccination due to the increased risk of adverse reactions to revaccination. The woman was susceptible to pertussis and diphtheria, and immune to measles, mumps and rubella. It was recommended that the woman should not receive tetanus toxoid and a new serological evaluation would be done 10 years after, in order to support the decision about revaccination.

Adult↗
PubMedDate not supplied

Prevalence of hyperimmunization against tetanus in Italians born after the introduction of mandatory vaccination of children with tetanus toxoid in 1968.

Systematic mandatory immunization of children against tetanus was started in Italy in 1968. Prevalence of tetanus hyperimmunization (> 5 IU/ml) was assessed among 214 immune subjects born after 1968 and found to be 17.3%. This figure is significantly higher (p < 0.01) than the 10.8% found in a previous study of subjects born before 1968. This increase is statistically significant in the Center (p < 0.01) and in the South (p < 0.05) of Italy, but not in the North. Hyperimmunization is not associated with family size (odds ratio 2.16; C. I. 95% = 0.5-7.6) or the father's years of education (odds ratio 1.83; C. I. 95% = 0.6-5.3). No difference was found between urban and rural areas of residence. Indiscriminate administration of booster doses of tetanus vaccine in hyperimmune subjects in some areas could result in unnecessary vaccinations, which can cause hypersensitivity reactions.

Adolescent↗
PubMed1981

Response to single dose of tetanus vaccine in subjects with naturally acquired tetanus antitoxin.

Tests among 410 Indians not artificially immunised against tetanus showed that 80% had measurable antitoxin. Single doses (100 Lf or 250 Lf) of a potent tetanus toxoid were given to such individuals with naturally acquired antitoxin. The 100 Lf dose produced on average a ten-fold rise in antibody level, and the 250 Lf dose a twenty-fold rise. In adults who had been artificially immunised, a 5 Lf dose produced a four-fold to ten-fold rise in antibody level. In infants three doses of triple vaccine produced satisfactory antitoxin concentrations. The levels of antibody achieved after a single 250 Lf dose should protect for 5 years. Single-dose vaccination may be better than the conventional three-dose scheme for a population that is unlikely to comply with a three-dose regimen and in whom naturally acquired antitoxin is associated with partial tolerance to tetanus toxoid. Naturally acquired antitoxin in Indians is probably the result of chronic clostridial contamination of the small bowel. This contamination can induce immune tolerance in the gut and systemically and may be the reason for the poor responses to vaccination in all except infants.

Adult↗
PubMed2001

Magnitude of interference after diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b capsular polysaccharide-tetanus vaccination is related to the number of doses administered.

We compared the antibody response to Haemophilus influenzae type b capsular polysaccharide (PRP) after 1, 2, or 3 doses of a diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine combined with a PRP-tetanus conjugate (PRP-T) vaccine, followed by separate injections of DTaP and PRP-T vaccines for the last 1 or 2 doses. Healthy infants were recruited from pediatric practices and were immunized according to recommended schedules. A significant decrease in the mean anti-PRP (from 5.25 to 2.68 microg/mL) and anti-tetanus toxoid antibody responses (from 0.13 to 0.09 Eq/mL) was observed as the number of doses of the DTaP/PRP-T combination vaccine increased (P<.02 and P=.01, respectively). In contrast, the mean anti-diphtheria toxoid antibody response increased with increasing numbers of DTaP/PRP-T doses (P=.0001). The effects of interference were not eliminated by the completion of the primary series with 1 or 2 doses of the DTaP and PRP-T vaccines given separately.

Antibodies, Bacterial↗
PubMed1999

Safety and immunogenicity of Haemophilus influenzae-tetanus toxoid conjugate vaccine given separately or in combination with a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine for the first four doses.

The purpose of this randomized, controlled trial was to assess the safety and immunogenicity of a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine given either separately or combined as a single injection with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine. A total of 180 infants were immunized at 2, 4, and 6 months of age; 129 were given a booster dose at 16-19 months of age. Vaccine-associated adverse events were similar whether the vaccines were combined as a single injection or given separately. There were no differences in levels of antibodies to Bordetella pertussis antigens (pertussis toxoid, filamentous hemagglutinin, and pertactin), diphtheria toxoid, or the three poliovirus types. The tetanus antitoxin level after the primary three-dose series was higher in recipients of the combined vaccine (2.37 IU/mL) than in recipients of the separate injections (1.32 IU/mL; two-sided P = .0001). In contrast, combined vaccine recipients had lower levels of antibody to H. influenzae type b polysaccharide after the third dose (1.57 microg/mL) than did those given separate injections (3.22 microg/mL; two-sided P = .0026). The antibody levels were not significantly different before or 1 month after the booster dose (32.9 microg/mL vs. 47.8 microg/mL, respectively; two-sided P = .07). We conclude that the vaccines were immunogenic and well tolerated. Despite lower levels of antibody to the H. influenzae type b polysaccharide after the primary three-dose series, mixing of the vaccines in a single syringe likely induced immunologic priming, as suggested by the high antibody levels after the booster dose.

Antibodies, Bacterial↗