Anti-tetanus Antibody Research Articles

Detection of Anti-Tetanus Antibodies in Turkish Population

Detection of Anti-Tetanus Antibodies in Turkish Population

Immunoglobulin G (IgG) subclass distribution and IgG1 avidity of antibodies in human immunodeficiency virus-infected individuals after revaccination with tetanus toxoid.

In human immunodeficiency virus (HIV)-infected individuals the amount of antibodies formed after vaccination with T-cell-dependent recall antigens such as tetanus toxoid is proportional to the peripheral blood CD4(+) T-lymphocyte counts. To investigate whether the immunoglobulin G (IgG) subclass distribution and avidity of the antibodies produced after vaccination are affected as well, we gave 13 HIV-infected adults with low CD4(+) T-lymphocyte counts (<200 x 10(6)/liter; group I), 11 HIV-infected adults with intermediate CD4(+) T-lymphocyte counts (>/=200 x 10(6)/liter; group II), and 5 healthy controls booster immunizations with tetanus toxoid. The prevaccination antibody concentrations against tetanus toxoid were similar in the HIV-infected and healthy adults. After vaccination the total IgG and the IgG1 anti-tetanus toxoid antibody concentrations were significantly lower in group I than in group II and the controls. The avidity of the IgG1 anti-tetanus toxoid antibodies formed by HIV-infected adults was within the range for healthy controls, irrespective of their CD4(+) T-lymphocyte counts.

Susceptibility to tetanus and missed vaccination opportunities in Portuguese women

Maternal and cord sera (96 pairs) were tested to measure antitetanus toxin IgG (ATT IgG) levels, using a commercial enzyme immunoassay. One mother had no detectable antitetanus antibody and four more had levels below those considered to be reliably protective (<160 mIU/ml). All five had been eligible for vaccination during pregnancy according to Portuguese guidelines, although one had received seven lifetime doses of TT. In maternal and cord sera, ATT IgG levels among those not vaccinated during the current pregnancy were significantly lower than among vaccinees ( p<0.0001), but there was no difference between those vaccinated once or twice during pregnancy. Among those not vaccinated during pregnancy, levels of ATT IgG decreased with time since last dose of vaccine ( P=0.0001). The total number of doses of vaccine was not significantly associated after controlling for time since last dose. Missed immunization opportunities occurred among half the women studied. Efforts to sustain protection against tetanus must be intensified.

Transcutaneous immunization with bacterial ADP-ribosylating exotoxins as antigens and adjuvants.

Transcutaneous immunization (TCI) is a new technique that uses the application of vaccine antigens in a solution on the skin to induce potent antibody responses without systemic or local toxicity. We have previously shown that cholera toxin (CT), a potent adjuvant for oral and nasal immunization, can induce both serum and mucosal immunoglobulin G (IgG) and IgA and protect against toxin-mediated mucosal disease when administered by the transcutaneous route. Additionally, CT acts as an adjuvant for coadministered antigens such as tetanus and diphtheria toxoids when applied to the skin. CT, a member of the bacterial ADP-ribosylating exotoxin (bARE) family, is most potent as an adjuvant when the A-B subunits are present and functional. We now show that TCI induces secondary antibody responses to coadministered antigens as well as to CT in response to boosting immunizations. IgG antibodies to coadministered antigens were also found in the stools and lung washes of immunized mice, suggesting that TCI may target mucosal pathogens. Mice immunized by the transcutaneous route with tetanus fragment C and CT developed anti-tetanus toxoid antibodies and were protected against systemic tetanus toxin challenge. We also show that bAREs, similarly organized as A-B subunits, as well as the B subunit of CT alone, induced antibody responses to themselves when given via TCI. Thus, TCI appears to induce potent, protective immune responses to both systemic and mucosal challenge and offers significant potential practical advantages for vaccine delivery.

Defective immune response to tetanus toxoid in hemodialysis patients and its association with diphtheria vaccination

The incidence of infectious diseases is increased in patients with chronic renal failure. This is thought to be due to an impaired T cell stimulation by antigen presenting cells. Immunization programs are of great significance in the prevention of infections in immunocompromised individuals. However, the immune response to various vaccinations is impaired in patients with chronic renal failure. So far only few studies have focused on seroresponse to tetanus toxoid. Therefore we measured the levels of anti-tetanus toxoid antibodies in 71 hemodialysis patients with unknown vaccination history. The antibody levels were detected prior to and twelve months after a single “Td” or “Td–d–d” vaccination. Initially only 31 (44%) of the patients had a sufficient protection against tetanus. Of the unprotected patients 15 (38%) seroconverted after immunization, while 25 (63%) did not respond. We found a high association ( p<0.04, Fisher's exact test) between the efficacy of vaccination against diphtheria and tetanus. Out of 38 initially unprotected patients 27 (71%) showed a similar response to both vaccines: 9 (24%) individuals seroconverted, while 18 (47%) did not. Our data clearly demonstrate the need for frequent monitoring of antibody levels after immunization against tetanus and diphtheria in hemodialysis patients.

Feasibility studies of large scale production of human anti-tetanus toxoid monoclonal antibodies

The feasibility of large scale production of human anti-tetanus toxoid monoclonal antibody for therapeutic use was evaluated using a human heterohybridoma. The effects of duration of subculture, transition from static to agitated culture conditions and the level of serum concentration were studied. The level of antibody secreted by the clone decreased with increasing length of subculture and decreasing serum concentration. The clone exhibited heterogeneity in expression of surface IgG after 2 or 7 weeks of subculture in static culture conditions irrespective of the serum concentration. However, a prolonged duration of subculture (9 weeks) in 3% serum medium had an effect on the expression of surface IgG both in static and agitated culture conditions. With respect to total (surface and intracellular) IgG, two distinct cell populations were observed. On long term subculture (9 weeks) in low serum medium (3% FCS), there was a decrease in the population which was the high synthesizer. In addition, when these cells were cultivated in agitated spinner flasks, a defect in secretion of antibodies was observed. Thus a general fall in the amount of antibody in the supernatant of agitated cultures was due to decrease in antibody synthesis as well as the defect in secretion of antibodies.

A typical bacterial ornithine-containing lipid Nalpha-(D)-[3-(hexadecanoyloxy)hexadecanoyl]-ornithine is a strong stimulant for macrophages and a useful adjuvant.

Nalpha-[3-(Hexadecanoyloxy)hexadecanoyl]-ornithine is a typical bacterial ornithine-containing lipid (OL). The configuration of the 3-hydroxy fatty acids in the OL was proved to be D by using HPLC with chiral column. For this analysis, Nalpha-(D or L)-[3-(hexadecanoyloxy)hexadecanoyl]-L-ornithine were synthesized and used as standards. The typical bacterial OL, as well as the synthesized one, exhibited strong interleukin-1- and prostaglandin E2-inducing activities, and further, it induced the production of high IgG anti-tetanus toxoid antibodies in mice. The typical OL is expected to be utilized as a nontoxic, potent adjuvant.

A typical bacterial ornithine-containing lipid N α-( d)-[3-(hexadecanoyloxy)hexadecanoyl]-ornithine is a strong stimulant for macrophages and a useful adjuvant

N α -[3-(Hexadecanoyloxy)hexadecanoyl]-ornithine is a typical bacterial ornithine-containing lipid (OL). The configuration of the 3-hydroxy fatty acids in the OL was proved to be d by using HPLC with chiral column. For this analysis, N α -( d or l)-[3-(hexadecanoyloxy)hexadecanoyl]- l-ornithine were synthesized and used as standards. The typical bacterial OL, as well as the synthesized one, exhibited strong interleukin-1- and prostaglandin E 2-inducing activities, and further, it induced the production of high IgG anti-tetanus toxoid antibodies in mice. The typical OL is expected to be utilized as a nontoxic, potent adjuvant.

Urinary loss of immunoglobulin G anti-F(ab′) 2 and anti-DNA antibody in systemic lupus erythematosus nephritis

The objective of this study was to determine whether the low levels of serum immunoglobulin G (IgG) anti-F(ab′) 2 seen in some patients with active systemic lupus erythematosus (SLE) were directly related to the deposition of antibody with this specificity in the kidney or alternatively to the urinary loss of IgG anti-F(ab′) 2. Serum Levels of IgG anti-F(ab′) 2, anti-tetanus toxoid, and anti-ds DNA antibody were measured in parallel with urinary excretion of these same 3 antibodies in 28 patients with SLE nephritis and in 28 control patients with other forms of chronic kidney disease. Low levels of both serum IgG anti-F(ab′) 2 or anti-tetanus antibody appeared to correlate with increased levels of urinary loss of these same antibodies in some patients with SLE and in control subjects with kidney disease. However, urinary loss could not account for low serum levels of either IgG antibody in many subjects. Quantitative 24-hour urinary losses of IgG anti-F(ab′) 2 and anti-DNA were much higher in patients with SLE than in control subjects with kidney disease ( P < .05), whereas amounts of IgG urinary loss of anti-tetanus were similar in patients with SLE and in control subjects. In nearly 1 third of SLE nephritis patients, 13% to 53% of total excreted urinary IgG showed anti-DNA enzyme-linked-immunosorbent assay reactivity. Urinary IgG in many patients with SLE showed both anti-DNA and anti-F(ab′) 2 reactivity, but dual anti-DNA/F(ab′) 2 specificity was more pronounced in affinity-isolated serum IgG anti-DNA or anti-F(ab′) 2 than in excreted urinary IgG molecules. The affinity of urinary IgG for either DNA or F(ab′) 2 was much lower than the same antibody activities measured either in serum or in kidney biopsy eluates. When the relative affinity of anti-DNA antibody in serum, urine, and kidney biopsy eluate was measured in parallel, the highest affinity antibody was found in kidney biopsy eluates, followed by serum antibody with urine antibody affinity showing the lowest values. These findings suggest a relative concentration of the highest affinity, doubly reactive IgG anti-DNA/F(ab′) 2 in SLE kidney tissues during SLE nephritis and implicate this process as an important factor in ongoing tissue damage.

Immunologic Response to Tetanus Toxoidin the Elderly: One-Year Follow-Up

Study objective: To determine whether elderly patients documented to have nonprotective titers of anti-tetanus antibodies (ATA) are able to achieve and maintain protective ATA titers for at least 1 year after tetanus immunization. Methods: Thirty-five outpatients aged 65 or older with documented inadequate ATA titers were given 1 tetanus immunization. Repeat titers were obtained 2 months and 12 months after immunization. Titers were measured with an enzyme-linked immunoassay kit (Bindazyme kit). ATA titers in excess of .17 IU were considered protective. The study was conducted at a large urban geriatric center. Results: The mean age of participants was 78.7 years; 86% (24/28) were women. Repeat ATA titers were obtained an average of 122 days and 493 days after immunization. The mean preimmunization ATA titer was .1 IU, (range .04 to .16 IU). After immunization, the 2-month ATA titer rose a mean of .61 (95% confidence interval [CI] .35 to .87) IU, with 86% (30/35) achieving protective titers. After 1 year only 28 of 35 patients were available for follow-up. Protective titers had been present in all 7 patients lost to follow-up. After 1 year, 82% (23/28) patients had protective titers. The mean ATA titer for the 28 patients was .54 (95% CI –.78 to 1.86) IU, a significant increase from preimmunization levels ( P=.002). However, ATA titers changed –.18 (95% CI –.98 to .62) IU between 2 months and 1 year ( P=.02). There was no correlation between gender, country of birth, and medical history with development or maintenance of protective titers. Conclusion: Administration of 1 tetanus toxoid affords protective immunization to a large portion of the elderly population after 1 year. [Alagappan K, Rennie W, Lin D, Auerbach C: Immunologic response to tetanus toxoid in the elderly: One-year follow-up. Ann Emerg Med August 1998;32:155-160.]

Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants.

The plethora of newly discovered vaccines implies that, in the future, many vaccines will have to be administered simultaneously to infants. We examined the potential interference with the immune response of several coadministered vaccines containing the same protein component, namely, tetanus toxoid (TT). Infants simultaneously receiving a tetravalent pneumococcal vaccine conjugated to TT (PncT) and a diphtheria-tetanus-pertussis-poliovirus-Haemophilus influenzae type b-tetanus conjugate vaccine showed significantly lower anti-H. influenzae type b polysaccharide (polyribosylribitol phosphate [PRP]) antibody concentrations than those receiving either a tetravalent pneumococcal vaccine conjugated to diphtheria toxoid or placebo. A dose range study showed that anti-PRP antibody concentrations were inversely related to the TT content of the PncT vaccines administered in infancy. Postimmunization antitetanus antibody concentrations were also affected adversely as the TT content of the coadministered vaccines was increased. This phenomenon, which we believe derives from interference by a common protein carrier, should be taken into account when the introduction of an immunization program including multiple conjugate vaccines is considered.

Optimisation of human anti-tetanus toxoid antibody responses and location of human cells in SCID mice transplanted with human peripheral blood leucocytes

A strategy for the production of human antibodies to tetanus toxoid (TT) is described. Human peripheral blood lymphocytes (PBL) were injected into severe combined immunodeficient (SCID) mice (termed hu-PBL-SCID) and the mice subsequently immunised with purified TT. By using low immunising doses of antigen, PHA activated PBL and PBL from donors who were recently immunised with TT, we established ongoing antibody responses to TT with specific recall IgG responses of up to 22 IU ml-1 in the murine plasma, which was greater than that in the donors' serum. Total IgG concentrations of up to 6 mg ml-1 were detected over a 32 week period. Lower levels of IgM and IgM anti-TT were also detected over this time. Large cellular infiltrations of human CD45+ and CD20+ cells were detected by immunocytochemistry in the mesenteric membranes, mesenteric lymph nodes and the pancreas 5 weeks after PBL were engrafted into a SCID mouse. Human cells were also observed in the lungs, liver, thymus and spleen. Cells isolated from the tissues were cultured with Epstein-Barr virus and the resulting B-cell lines produced Ig in vitro up to 7 weeks, with IgG and IgM anti-TT detected transiently in a culture of cells from the mesenteric membranes.

The effect of dexamethasone on immunological memory to tetanus toxoid in sheep

One of two groups of sheep was immunosuppressed with the glucocorticoid, dexamethasone, at the time of the first but not of the second of two booster vaccinations with tetanus toxoid given at an interval of 28 days. Treatment with dexamethasone decisively reduced the anti-tetanus antibody response to the first booster vaccination and affected both IgM and IgG1 antibody. However, antibody titres increased after the second booster vaccination in the treated sheep and were similar in size to those in the untreated sheep which rose in stepwise fashion after each booster vaccination. The differences in response imply that processes involved in displaying an anamnestic response and recalling previously established memory are sensitive to glucocorticoids. Accordingly, they can be separated from the glucocorticoid-resistant processes that lead to the expansion of immunological memory following multiple exposures to an antigen.

Improved ELISA for determination of anti-diphtheria and/or anti-tetanus antitoxin antibodies in sera.

Double-antigen ELISAs for detection and quantification of anti-tetanus or anti-diphtheria antibodies in serum have been developed. The assays showed good correlations with established toxin neutralizing assays and were functionally specific for IgG antibodies. The double-antigen set-up allows specific antibodies to bind to antigen-coated microtitre wells with one arm and the free arm to bind to biotin-labelled antigen. The amount of antibodies able to bind labelled antigen was assessed by adding enzyme-conjugated streptavidin and colour substrate followed by measurement of the colour using an ELISA reader. The double-antigen principle makes it possible to compare samples of different species on the same plate, permitting the direct use of existing international references of animal or human origin. The double-antigen ELISAs showed a detection limit of 0.00002 IU/ml for both antibodies and were suitable for quantifying antibodies in blood samples collected on filter paper as well as in serum. The assays required no special equipment compared to traditional ELISA.

Assessment of avidity of anti-tetanus toxoid antibodies to evaluate the reconstitution of humoral immunity after allogeneic bone marrow transplantation

Assessment of avidity of anti-tetanus toxoid antibodies to evaluate the reconstitution of humoral immunity after allogeneic bone marrow transplantation

Assessment of avidity of anti-tetanus toxoid antibodies to evaluate the reconstitution of humoral immunity after allogeneic bone marrow transplantation

Assessment of avidity of anti-tetanus toxoid antibodies to evaluate the reconstitution of humoral immunity after allogeneic bone marrow transplantation

Immunization of mice with poliovirus replicons expressing the C-fragment of tetanus toxin protects against lethal challenge with tetanus toxin

In this study, we describe the construction of poliovirus genomes or “replicons” which contain the C fragment gene of tetanus toxin substituted for the poliovirus P1 capsid. Upon transfection of replicon RNA into cells, we immunoprecipitated a protein corresponding to the C-fragment of tetanus toxin using tetanus-specific antibodies. Using a recombinant vaccinia virus expressing poliovirus P1 capsid protein (VV-P1) to provide P1 protein, the replicon RNA was encapsidated; stocks of the replicons were generated by passage with VV-P1. The immunogenicity of the replicons was determined by immunization of transgenic mice which are susceptible to poliovirus. A serum antibody response to poliovirus and tetanus toxoid was detected in all of the immunized mice. Protection against a lethal dose of tetanus toxin generally correlated with the levels of serum anti-tetanus antibodies. To address whether pre-existing antibodies to poliovirus limit the effectiveness of the replicon as a vaccine vector, mice were first immunized with the inactivated poliovirus vaccine followed by immunization with the replicons expressing C-fragment protein. Anti-tetanus antibodies were detected in these mice after a single administration of the replicon; these antibodies conferred protection upon challenge with tetanus toxin. These results demonstrate the potential use of poliovirus replicons encoding foreign proteins to induce a protective antibody response, even in the presence of pre-existing antibodies to poliovirus.

Effect of rIL-2 treatment on anti-tetanus toxoid response in the elderly

To explore the effects of interleukin-2 (IL-2) treatment in a vaccination protocol in the elderly, we administered low-dose rIL-2 to a group of aged subjects before primary tetanus toxoid immunization. A specific antibody response was detectable in the serum of 6/8 treated individuals after primary immunization, but in only 2/6 untreated controls; following antigenic boosting, specific antibody levels remained relatively unchanged in all the seroconverters. The data were confirmed by studying the ability to produce tetanus-specific antibodies in vitro, and by isoelectrofocusing analysis of serum anti-tetanus antibodies; this latter study showed a more restricted clonal response to the immunogen in untreated individuals. On the other hand, the study of the in vitro proliferative response to tetanus toxoid did not evidence clear differences between the two groups. On the whole, these data seem to indicate that a short-term rIL-2 treatment is able to potentiate the antibody response to tetanus toxoid, and may be a useful tool to improve humoral responses to vaccines in aged subjects.

Immune response to a combined hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine administered to infants at 2, 4 and 6 months of age

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6–12 weeks of age) received three doses of DTPw—HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU ml −1], anti-diphtheria and antitetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.

Rates of tetanus protection and transplacental tetanus antibody transfer in pregnant women from different socioeconomic groups in Peru.

In developing countries, neonatal tetanus causes significant mortality. Using a new competitive enzyme-linked immunosorbent assay to measure anti-tetanus toxin antibody levels, we compared rates of protection, total antibody levels, and maternal-to-fetal antibody ratios between different socioeconomic groups in Peru. Upper-middle-class women 25 years and older had significantly lower rates of protection and mean anti-tetanus toxin antibody levels than did lower-class women of the same age. Nevertheless, the former had higher fetal-to-maternal antibody ratios, independent of maternal age, total antibody levels, or parity. We conclude that future vaccination programs in Latin America must target upper-middle-class as well as lower-class women.