IgG Anti-tetanus Antibody Research Articles

Antibody levels following vaccination of beef calves with a tetanus toxoid

Tetanus is a preventable, yet often fatal, disease affecting many species, including beef cattle. Vaccination for tetanus is recommended for calves at high risk of disease, but typical beef cattle management practices often make adherence to vaccine manufacturers’ guidance for a second (booster) dose of vaccine difficult. This study examined the antibody response following a single dose of tetanus toxoid, as well as following booster vaccination at various intervals. Anti-tetanus IgG antibodies were detectable 25 days (D25) after a single dose, and rose following booster at either D25 D109 after initial vaccination. Antibody levels then declined numerically from D109 to D179 for calves boostered at D25 but rose on D179 for those receiving a second dose on D109. The relatively rapid response in IgG production, even in the absence of a booster vaccine, may suggest value in vaccinating calves for tetanus at time of greatest risk, even if a booster cannot be administered. The study also provides support for priming of the immune response lasting at least until D109 after primary immunization.

Immunogenicity and safety of a tetanus-diphtheria vaccine and a 13-valent pneumococcal conjugate vaccine after concomitant vaccination in\u2009\u2265\u200950-year-old adults

BackgroundWhen two or more vaccines are administered concurrently, there is concern about safety and immunogenicity from vaccine interaction.MethodsSubjects aged ≥50 years were randomized 1:1:1 to receive tetanus-diphtheria (Td) + 13-valent pneumococcal conjugate vaccine (PCV13; Group 1), PCV13 alone (Group 2), or Td alone (Group 3). After single or concomitant vaccination, enzyme-linked immunosorbent assay and opsonophagocytic assay (OPA) were performed to compare immunogenicity for Td and PCV13, respectively.ResultsA total of 448 subjects were available for the assessment. After concomitant administration, the non-inferiority criteria of geometric mean titer (GMT) ratios were met for tetanus, diphtheria, and all four pneumococcal serotypes (1, 5, 18C, and 19A). However, subjects in Group 3 (Td alone) were more likely to have a high IgG anti-tetanus antibody titer (≥ 0.5 U/mL) than those in Group 1 (Td + PCV13) (p < 0.01). As for the pneumococcal serotype 1, the OPA GMT was significantly higher in Group 1 (PCV13 + Td) compared to Group 2 (PCV13 alone) (p = 0.02). No serious adverse event occurred.ConclusionsConcomitant Td and PCV13 administration induced sufficient immunity without significant interference and showed good safety profiles.Trials registrationNCT03552445 registered at http://www.clinicaltrials.gov on June 11, 2018 (retrospectively registered).

Tetanus immunisation in a cohort of adults seen in an accident and emergency unit of a tertiary health facility in Nigeria

Background: Tetanus remains a major health problem in many developing countries including Nigeria. Most cases of tetanus in the developing countries are in the young people under 40 years. In view of the high mortality from tetanus, prevention remains the best form of treatment. Objective: The objective was to determine the effectiveness of anti-tetanus immunisation in a cohort of Nigerian adult population. Methods: Patients with open injuries and controls without open injuries were investigated. Blood samples for IgG Anti-Tetanus Antibody (ATAb) assessments were taken from patients and controls on admission before giving anti-tetanus toxoid (ATT) and at 4 weeks later. Serum ATAb was quantitated using Tetanus Toxoid IgG ELISA Kit (Demeditec Diagnostics, Germany). ATAb results were expressed in International Units per millilitre (IU/mL). ATAb levels > 0.1 IU/mL were considered protective. Results: A total of 159 patients and 90 controls were studied. The mean of ATAb patient was 1.13 (2.37) IU/mL, higher than the mean of 0.76 (1.4) IU/mL) in controls. In both the patients and controls, females had higher baseline ATAb levels; this was statistically significant in controls (P 8-fold and the percentage of patients that required immunisation dropped from 47.2% to 10%. Although 11 (30%) patients had a history of ATT, their serum ATAb was not higher than those who did not have a history of ATT - 1.02 (1.51) IU/mL and 1.19 (2.67) IU/mL, respectively. Conclusion: There was a good response to ATT immunisation. Therefore, anti-tetanus immunisation should be continued in hospitals.

Diphtheria in Lao PDR: Insufficient Coverage or Ineffective Vaccine?

BackgroundDuring late 2012 and early 2013 several outbreaks of diphthe-ria were notified in the North of the Lao People’s Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions.MethodsA serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12–59 months. Serum samples, socio-demographic data, nutri-tional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA.ResultsOverall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4–28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74–85, 4], p = 0.01) and the lack of advice on vac-cination given at birth (OR: 9.8 [95% CI: 1.5–63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008–0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status.ConclusionsOur data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical defi-ciencies in the methods of storage and distribution of vaccines as well as unreliability of vac-cination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against diphtheria and recommendations are provided to prevent future outbreaks.

Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor.

Engagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. The aim of this study was to characterize B cell immunosuppression mediated by the Fc-engineered antibody, XmAb5871, which coengages FcγRIIb with the B cell antigen receptor (BCR) complex and that is currently in clinical development for the treatment of rheumatoid arthritis (RA). Because rheumatoid factor (RF) might interfere with the binding of XmAb5871 to FcγRIIb, we correlated RF titers with the potency of XmAb5871. We analyzed the expression of CD19, FcγRIIb, and CD86 on naive and memory B cells from 50 patients with RA and 66 healthy donors, quantified XmAb5871-induced promotion of FcγRIIb phosphorylation and suppression of calcium flux in activated B cells, measured CD86 inhibition in whole blood, and correlated RF and anti-citrullinated protein antibody (ACPA) levels with drug potency. We engrafted RA peripheral blood mononuclear cells (PBMCs) into SCID mice, treated them with XmAb5871, and quantified human total IgG, total IgM, and anti-tetanus IgG antibody levels in vivo. B cells from all donors expressed CD19 and FcγRIIb, and the expression of FcγRIIb was higher on naive, but not memory, B cells from donors with RA compared with healthy donors. BCR-mediated calcium flux was suppressed by XmAb5871 and was associated with FcγRIIb phosphorylation. XmAb5871 inhibited CD86 induction, and the levels of RF and ACPAs did not affect efficacy. XmAb5871 suppressed B cell activation regardless of disease severity. In SCID mice engrafted with PBMCs from a patient with RA, XmAb5871 suppressed humoral responses. Coengagement of the BCR complex and FcγRIIb by XmAb5871 inhibits B cell activation and function. The similar potency in patients with RA and healthy donors and the absence of autoantibody interference suggest that XmAb5871 may represent a new therapeutic strategy to suppress autoreactive B cells in RA.

A Study on the Protection of Hemodialysis Patients Against Diphtheria and Tetanus

Patients with end stage renal disease suffer from a high incidence of infectious diseases believed to be related to their impaired immune system. To determine the antitetanus and antidiphtheria IgG antibody levels in Iranian hemodialysis patients with end stage renal disease, as well as its association with sex, age, hemoglobin, zinc serum level, serum albumin, duration of dialysis, number of dialysis per week, dialysis adequacy, erythropoietin or iron supplements such as venofer, body mass index (BMI), and underlying renal disorder, we conducted a cross-sectional study on a total of 112 hemodialysis patients with end stage renal disorder (60 male, 52 female ) and 36 healthy individuals in the control group (14 male, 22 female). The patients and the control group received no antitetanus or antidiphtheria vaccine or immunoglobulin in the year prior to the investigation. The serum antitetanus and antidiphtheria IgG antibody levels were measured using the ELISA method. We found out that only 16% of our hemodialysis patients were immune to diphtheria (19% of the control group), and this rate for tetanus was 24% (48.2% in the healthy control). Except for the hemodialysis duration, none of the mentioned factors seemed to affect immunity. We conclude that in our study, the level of the antitetanus IgG antibody (unlike the antidiphtheria IgG antibody level) is significantly different among the hemodialysis patients, the chronic hemodialysis patients, and the control group.

Evaluation of Anti-Tetanus Immunity in Haemodialysis Patients

Problem statement: The incidence of infectious diseases is increased in patients with chronic renal failure. Chronic renal failure severely influences the immune functions of the host. Approach: To evaluate the antitetanus immunity level in southern Iranian patients with end stage renal disease undergoing hemodialysis and to find its association with sex, age, blood hemoglobin and serum albumin, duration of dialysis. This cross sectional study was carried out on a total of 52 patients, who were on hemodialysis and 52 age and sex matched healthy individuals with without any underlying renal disease as a control group. Individuals in the both groups receiving antitetanus toxoid vaccine or immunoglubins a year prior to the study were excluded. The serum antitetanus IgG antibody levels were measured by an ELISA method. Results: Tetanus protected individuals in the patients and the control groups were 34.6 and 63.30% respectively. Of the evaluating factors just hemodialysis duration found to affect on tetanus immunity. Conclusion: Tetanus protected individuals in the patients group were significantly less than tetanus protected individuals in the control group (p = 0.011). Hemodialysis duration has significant effect on antitetanus immunity level.

Antitetanus toxoid antibody titer of chronic hemodialysis patients in Iran.

Patients with end stage renal disease have higher incidence of infection diseases that is thought to be related to impaired immune system. To determine the antitetanus IgG antibody level in Iranian hemodialysis patients with end stage renal disease and to find its association with sex, age, blood hemoglobin, serum albumin, duration of dialysis, time of dialysis per week, dialysis adequacy, erythropoietin, or iron supplementation, body mass index (BMI) and underlying renal disorder. We conducted a cross sectional study on a total of 108 Iranian hemodialysis patients with end stage renal disorder, and 36 healthy individuals in the control group matched with the patient group. The patients and controls did not receive any antitetanus vaccine or immunoglobulins a year prior to the investigation. The serum antitetanus IgG antibody levels were measured by an ELISA method. We found 74.3% of patients to have unprotected antitetanus IgG antibody level compared with 52.8% of the control group. Except hemodialysis duration, none of the contributing factors seemed to affect immunity. We conclude that in our study, there is a significant difference in the antitetanus IgG antibody level between hemodialysis patients and the control group and also in the chronic hemodialysis patients.

Reduced tetanus antibody titers in overweight children

Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO2 normalized to body weight. IL-6 was significantly higher in the obese children (2.6 ± 0.3 vs. 1.3 ± 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1β and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 ± 0.6 vs. 4.2 ± 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be due to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to the chronic low grade inflammation expressed by the higher levels of IL-6.Please click http://www.journalsonline.tandf.co.uk/openurl.asp?genre=article&issn=0891-6934&volume=39&issue=4&spage=349"here for an erratum concerning this article.

Biodegradable microspheres as controlled-release tetanus toxoid delivery systems

Purified tetanus toxoid, a high-molecular-weight protein, was entrapped within poly( L-lactic acid) (PLA) and poly( D, L-lactic/glycolic acid) (PLGA) microspheres prepared by either a solvent extraction or a solvent evaporation method carried out in a multiple emulsion system (water-in-oil-in-water). The physical integrity and antigenicity of the protein treated under different processing conditions were investigated. A reduction of antigenicity that was related to the percentage of aggregated protein was noticed under some experimental conditions. This partial loss of antigenicity was associated with the lyophilization process and affected by the nature of the organic solvent. All types of microspheres prepared with different molecular weight PLA and PLGA displayed a high protein-loading efficiency (>80%) but their size was strongly influenced by polymer molecular weight (3000 versus 100 000). Protein release pattern was influenced by both polymer molecular weight and composition (PLA versus PLGA). A constant release pattern after an induction period of 10 days was observed for microspheres composed of high-molecular-weight polymers (PLA and PLGA). The release rate was lower from PLA microspheres than from PLGA microspheres. In contrast, a continuously increasing release rate preceded by a burst was observed for low-molecular-weight (3000) PLGA microspheres. Microencapsulated tetanus toxoid was significantly more immunogenic in mice than fluid toxoid as determined by IgG anti-tetanus antibody levels and neutralizing antibodies. However, the magnitude and duration of the antibody response did not differ significantly from a similar dose of aluminium phosphate-adsorbed toxoid. We conclude that microencapsulated tetanus toxoid shows significant adjuvant activity. Further improvements in the formulation of microspheres which result in the release of higher concentrations of antigenically active tetanus toxoid for more prolonged periods may result in higher and more sustained antibody levels.

The construction and use of a human-mouse myeloma analogue suitable for the routine production of hybridomas secreting human monoclonal antibodies.

A human-mouse myeloma analogue termed HMMA2.11TG/O was constructed by fusion of the mouse myeloma cell line P3x63Ag8.653, a mutant derivative of MOPC21, with bone marrow mononuclear cells from a patients with IgA myeloma. The HMMA2.11TG/O cell line is resistant to 6-thioguanine and ouabain and sensitive to HAT. The cell line secretes no detectable immunoglobulin and has a hybrid karyotype and cell surface phenotype. An average fusion efficiency for growth of hybridomas of 1/17,000 fused cells was obtained in fusions with human peripheral blood mononuclear cells (PBM), Pokeweed Mitogen (PWM) stimulated PBM, and Epstein-Barr Virus (EBV) transformed polyclonal B cell lines. Over 75% of hybrids secrete detectable immunoglobulin and the cloning efficiency of the hybrids at 1 cell/well averages 25%. Antibody secreting cloned hybridoma cell lines were obtained by fusion directly with PBM from an immunized volunteer and by fusion with in vitro, secondarily immunized, EBV transformed polyclonal cell lines. Five hybridomas secreting human monoclonal IgM anti-tetanus antibodies and 2 secreting human monoclonal IgG anti-tetanus antibodies were selected and cloned from 6 fusions performed specifically for anti-tetanus antibody. Immunoglobulin and antibody secretion by cloned hybrids has been stable for 5-10 months at present. Immunoglobulin and antibody secretion in routine cultures passaged every 3-4 days has been 8-42 micrograms/ml. This human-mouse myeloma analogue should prove useful for the routine production of human monoclonal antibodies.

Human Anti‐F(ab′)2 Antibodies and Pepsin Agglutinators React with Fv Determinants

Affinity-purified human IgG anti-tetanus antibody was subjected to papain and then pepsin digestion, and residual fragments retaining antibody activity were re-isolated by adsorption and elution from Sepharose-tetanus toxoid columns. Both Fab' and Fv fragments isolated by gel filtration showed strong reactivity with anti-F(ab')2 antibodies. Failure of tetanus toxoid to completely block reactivity of anti-F(ab')2 antibody with anti-tetanus Fv fragments indicates that these antibodies react with framework antigens within variable antibody regions.

Production of antibody by human B cells under serum-free conditions

A method is described for growing human B cells in 20 μl hanging drops in Terasaki plates under serum-free conditions. B cell proliferation and differentiation has a critical dependence for added soybean lipid, while T cell proliferation does not. In this medium, pokeweed mitogen stimulation of separated human B cells induces high levels of immunoglobulin in a T dependent manner. Cells from donors vaccinated with tetanus toxoid and shown to be responders by a conventional culture system, produce high levels of IgG anti-tetanus antibody after antigen stimulation in these serum-free microcultures. The serum free culture system has the novel features of high sensitivity to dose of mitogen or antigen, low background responses and high antibody production with low cell numbers.

Expression of surface membrane IgG on pokeweed mitogen-reactive anti-tetanus toxoid antibody-producing cells.

Anti-tetanus toxoid antibody-producing cells, differentially expressing surface membrane IgM, were analyzed for the additional expression of surface membrane IgG. micron+ and micron- cells were rosetted with anti-gamma-ox red blood cells and separated by density centrifugation into fractions enriched or depleted of gamma + cells. These B-cell subsets were assayed for the production of IgM and IgG anti-tetanus toxoid antibody and total IgM and IgG. The results indicated that the majority of anti-tetanus toxoid antibody synthesis in the micron- fraction was by gamma + cells. In the microm+ fraction, however, both IgM and IgG anti-tetanus toxoid antibody production was detected in the micron+ gamma- and micron+ gamma+ fraction. The inclusion of isotype-specific antisera during the first 2 days of culture further established that gamma was expressed on the surface of the majority of the precursors for IgG anti-tetanus antibody production in vitro. Studies performed to determine the culture requirements of micron- and micron+ cells revealed that production of IgG anti-tetanus toxoid antibody by both cell subsets was dependent on T cells and pokeweed mitogen. However, some micron- cells could produce IgG in the presence of T cells alone.

Impaired generation of spontaneous and mitogen-reactive anti-tetanus toxoid antibody-producing B cells following repetitive in vivo booster immunization

Booster immunization of humans with tetanus toxoid generates a subpopulation of B lymphocytes in the blood which spontaneously synthesize IgG anti-tetanus antibody (anti-Tet). After repeat immunization 14 days later, subsequent lymphoblastoid cell responses were markedly decreased (21 to 37% of initial responses). This occurred whether the second immunization was given in the ipsilateral or contralateral arm. A third immunization at Day 28 failed to induce any lymphoblastoid cell response although serum anti-Tet antibody levels were equivalent to those at the time of the second immunization. The diminished IgG anti-Tet response seen after repeated immunization was correlated with a decreased precursor frequency of B cells producing IgG-anti-Tet. The inhibitory effect of repeated immunization was not simply a dose-related phenomenon as it was not mimicked by three tetanus boosters given at one time. Furthermore, it was antigen specific as IgG anti-diphtheria lymphoblastoid B cells could be induced while anti-tetanus cells were not. After three repetitive immunizations with tetanus toxoid, pokeweed mitogen (PWM)-inducible IgG anti-Tet responses were also inhibited. The mechanism for this was the loss of PWM-reactive B-cell activity and not the induction of excessive T suppression. This effect was also shown to be antigen specific as PWM-induced IgG anti-diphtheria responses were preserved. Thus repetitive immunization fails to continue to induce antigen-specific lymphoblastoid B cells and to inhibit the appearance of antigen-specific PWM-reactive cells. These events may be important in the observation that repeated immunization fails to continually increase antibody levels.

Antigen-induced suppression of human in vitro pokeweed mitogen-stimulated antibody production

Combinations of T and B lymphocytes from normal individuals booster immunized 14–30 days previously with a combination of diphtheria and tetanus toxoids, synthesized IgG antitetanus toxoid, and IgG antidiphtheria toxoid antibodies when stimulated by pokeweed mitogen in vitro. The addition of 5 μg of soluble tetanus toxoid to the cultures during the first 2 days incubation resulted in greater than 90% suppression of the subsequent production of IgG antitetanus toxoid antibodies. The synthesis of IgM antitetanus toxoid antibodies, total IgG, total IgM, and IgG antidiphtheria toxoid antibodies were unaffected. Similarly, the addition of 5 μg of soluble diphtheria toxoid suppressed the synthesis of IgG antidiphtheria toxoid antibodies with no effect on the synthesis of IgG antitetanus antibodies. Allogeneic combinations of B and T lymphocytes were capable of mediating the suppression, and irradiation of the T cells caused only a partial and variable reversal of the suppression. The antigen-induced specific suppression of antibody synthesis could not be demonstrated in cultures stimulated with soluble T-cell-derived helper factors.

Differential synthesis of IgM and IgG anti-tetanus toxoid antibody in vitro following in vivo booster immunization of humans

The in vitro syntheses of IgM and IgG anti-tetanus toxoid antibody by human peripheral blood leukocytes were compared prior to and at various intervals following in vivo booster immunization with soluble tetanus toxoid. Prior to booster immunization, the in vitro synthesis of IgG anti-tetanus toxoid antibody by combinations of B cells and irradiated T lymphocytes was negligible following pokeweed mitogen stimulation. Within 2 weeks after booster immunization, the quantity of IgG anti-tetanus toxoid antibody synthesized in vitro increased 5- to 20-fold. There was no comparable increase in total IgG synthesis. In contrast to the synthesis of IgG antibody, in vitro synthesis of IgM anti-tetanus toxoid antibody occurred prior to booster immunization and did not increase significantly following booster immunization. This dichotomy in anti-tetanus antibody production was further demonstrated in an individual with common variable hypogammaglobulinemia whose lymphocytes synthesized normal quantities of total IgG, IgM, and IgM anti-tetanus toxoid antibody in vitro, but failed to synthesize IgG anti-tetanus antibody following in vivo booster immunization.

IgE synthesis in man: II. Comparison of tetanus and diphtheria IgE antibody in allergic and nonallergic children

Specific IgE and IgG antibodies were quantitated in 91 allergic and 80 nonallergic age- and sex-matched children between 4 and 17 yr of age. Statistically significant increased antidiphtheria and antitetanus IgE antibodies (p < 0.01) measured by the radioallergosorbent test (RAST) were noted in allergic compared with nonallergic subjects. Of the allergic children with total serum IgE >500 U/ml, 19 of 52 (37%) and 25 of 52 (48%) had elevations (>2 SD above nonallergic control mean) of serum antitetanus or antidiphtheria IgE antibody, respectively, whereas only 2 of 35 allergic children with serum IgE <500 U/ml had elevation (>2 SD) of these antibodies. Antitetanus and antidiphtheria IgG antibodies were measured by passive sheep red blood cell (SRBC) hemagglutination. Geometric mean antitetanus IgG antibodies were higher in allergic (4.9 AU/ml) as compared to nonallergic (1.7 AU/ml) children (p < 0.001). Geometric mean antidiphtheria IgG antibodies were higher (0.31 AU/ml) in nonallergic and lower in allergic (0.10 AU/ml) subjects (p < 0.01). These data suggest that allergic individuals with markedly elevated total serum IgE have unique antibody responses following routine immunization with tetanus-diphtheria (Td) toxoids and tetanus-pertussis-diphtheria (DPT) which are manifest by enhanced specific IgE synthesis.