A possible explanation for the discrepancy between ELISA and neutralising antibodies to tetanus toxin

Dokmetjian, José Christian; Valle, C. Della; Lavigne, Victoria; Luján, Calcagno M. De; Manghi, Marcela Alejandra

doi:10.1016/s0264-410x(00)00066-9

Cited by 24 publications

(14 citation statements)

References 15 publications

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“…The MBA performed better than indirect ELISAs at low seroprotective antibody levels (0.01 to 0.2 IU/ml), allowing the use of a lower threshold of seroprotection (0.01 versus 0.1 to 0.2 IU/ml) (19)(20)(21)28). The MBA and DAE identified the same subpopulations with immunity gaps, where additional strengthening of RI services or TTCV SIAs may be required.…”

Section: Discussionmentioning

confidence: 97%

“…For in vitro assays of tetanus seroprotection, gold standards are the DAE (double-antigen enzyme-linked immunosorbent assay [ELISA]) and toxin binding inhibition (ToBI) tests, which are not commercially available (15)(16)(17)(18)(19). Indirect tetanus ELISAs exist, but they overestimate antibody levels in the low seroprotective range (0.01 to 0.2 IU/ml) (15,(19)(20)(21). For use in serosurveys, multiplex bead assays (MBAs) are promising, since antibody responses to many pathogens can be measured simultaneously by using minimal serum sample volumes.…”

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confidence: 99%

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Tetanus Immunity among Women Aged 15 to 39 Years in Cambodia: a National Population-Based Serosurvey, 2012

Scobie

Mao

Sokhal

et al. 2016

Clin Vaccine Immunol

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gTo monitor progress toward maternal and neonatal tetanus elimination (MNTE) in Cambodia, we conducted a nationwide serosurvey of tetanus immunity in 2012. Multistage cluster sampling was used to select 2,154 women aged 15 to 39 years. Tetanus toxoid antibodies in serum samples were measured by gold-standard double-antigen enzyme-linked immunosorbent assay (DAE) and a novel multiplex bead assay (MBA). Antibody concentrations of >0.01 IU/ml by DAE or the equivalent for MBA were considered seroprotective. Estimated tetanus seroprotection was 88% (95% confidence interval [CI], 86 to 89%); 64% (95% CI, 61 to 67%) of women had antibody levels of >1.0 IU/ml. Seroprotection was significantly lower (P < 0.001) among women aged 15 to 19 years (63%) and 20 to 24 years (87%) than among those aged >25 years (96%), among nulliparous women than among parous women (71 versus 97%), and among those living in the western region than among those living in other regions (82 versus 89%). The MBA showed high sensitivity (99% [95% CI, 98 to 99%]) and specificity (92% [95% CI, 88 to 95%]) compared with DAE. Findings were compatible with MNTE in Cambodia (>80% protection). Tetanus immunity gaps should be addressed through strengthened routine immunization and targeted vaccination campaigns. Incorporating tetanus testing in national serosurveys using MBAs, which can measure immunity to multiple pathogens simultaneously, may be beneficial for monitoring MNTE.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Tetanus Immunity among Women Aged 15 to 39 Years in Cambodia: a National Population-Based Serosurvey, 2012

Scobie

Mao

Sokhal

et al. 2016

Clin Vaccine Immunol

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“…In the evaluation of Ab responses to toxoid vaccines, the correlation between the affinity of Ab and serum neutralization is established (36,37). More recently, a particularly elegant and thorough study using recombinant Abs to the protective Ag of anthrax toxin and surface plasmon resonance firmly demonstrated that the ability of Ab to protect macrophages from cytotoxic effect and rats from lethality was directly correlated with Ab affinity (38).…”

Section: Discussionmentioning

confidence: 99%

Immunological Characteristics Associated with the Protective Efficacy of Antibodies to Ricin

Maddaloni

Cooke

Wilkinson

et al. 2004

The Journal of Immunology

109

147

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A/B toxins, produced by bacteria and plants, are among the deadliest molecules known. The B chain binds the cell, whereas the A chain exerts the toxic effect. Both anti-A chain and anti-B chain Abs can neutralize toxins in vivo and in vitro. B chain Abs block binding of the toxin to the cell. It is not known how anti-A chain Abs function. Working with ricin toxin, we demonstrate that immunization with A chain induces greater protection than immunization with B chain. A panel of mAbs, binding to A chain, B chain, or both chains, has been produced and characterized. Immunologic characteristics evaluated include isotype, relative avidity, and epitope specificity. The ability to inhibit ricin enzymatic or cell binding activity was studied, as was the ability to block ricin-mediated cellular cytotoxicity on human and murine cell lines. Finally, the in vivo protective efficacy of the Abs in mice was studied. The Ab providing the greatest in vivo protective efficacy was directed against the A chain. It had the greatest relative avidity and the greatest ability to block enzymatic function and neutralize cytotoxicity. Interestingly, we also obtained an anti-A chain Ab that bound with high avidity, blocked enzymatic activity, did not neutralize cytotoxicity, and actually enhanced the in vivo toxicity of ricin. Anti-A chain Abs with moderate avidity had no in vivo effect, nor did any anti-B chain Abs.

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“…Good correlation between the indirect ELISA and neutralization assays has been demonstrated, although this is ‫املتوسط‬ ‫لرشق‬ ‫الصحية‬ ‫املجلة‬ ‫عرش‬ ‫الثامن‬ ‫املجلد‬ ‫السادس‬ ‫العدد‬ generally when antibody concentrations are above 0.16-0.2 IU/mL [18]. Indirect ELISA, however, overestimates titres lower than this range when compared to the neutralization assay [19]. An antitoxin concentration above 0.15 IU/mL is the preferred correlate of protection based on the results of ELISA [8,20], which was applied in our study as a cut-off point between immune and non-immune cases.…”

Section: Discussionmentioning

confidence: 97%

Seroprevalence of tetanus antibodies among pregnant women in Duhok Governorate, Iraq

Hurmez¹,

Qs²,

Na³

2012

East Mediterr Health J

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Maternal immunization with tetanus toxoid (TT) is the most effective was to prevent neonatal tetanus. In Duhok, Iraq data indicate low vaccination coverage. This study assessed TT immunization status among 600 randomly selected pregnant women attending Azadi teaching hospital, Duhok for delivery, by both tetanus antibody seroprevalence and TT history. WHO criteria for protective levels were used for seroprevalence and vaccination history. Overall, 90% of the women at delivery had protective tetanus antitoxin titres compared to only 55% considered protected according to their vaccination history. Immunity rates for women who had received no TT vaccination, 1 dose, 2 doses and ≥ 3 doses were 28.0%, 92.6%, 100.0% and 99.0% respectively. Groups with lower serological immunity levels were women aged less than 25 years, those reporting no history of vaccination and those living in Akre, Bardarash or Shekhan districts of Duhok. Tetanus immunity determined by seroprevalence of tetanus antitoxin levels exceeded that estimated by vaccination history, and serological markers should be used instead of vaccination history in determining immunity status. RÉSUMÉ La vaccination des mères par l'anatoxine tétanique est la méthode la plus efficace de prévention du tétanos néonatal. À Duhok (Iraq), les données indiquent que la couverture vaccinale est faible. La présente étude a évalué le statut vaccinal pour l'anatoxine tétanique de 600 femmes enceintes sélectionnées aléatoirement et consultant l'hôpital universitaire Azadi à Duhok, pour leur accouchement. La méthode ELISA a permis de déterminer la séroprévalence de l'anatoxine tétanique et les antécédents des patientes en la matière. Les critères de l'Organisation mondiale de la Santé pour les taux protecteurs ont été utilisés pour la séroprévalence et les antécédents de vaccination. Globalement, 90 % des femmes à l'accouchement avaient des titres d'antitoxine tétanique protecteurs par rapport à seulement 55 % des femmes considérées comme protégées selon leurs antécédents de vaccination. Les taux d'immunité chez les femmes n'ayant pas reçu de vaccination antitétanique, ou ayant reçu une dose, deux doses ou trois doses ou moins représentaient 28,0 %, 92,6 %, 100,0 % et 99,0 % respectivement. Les groupes présentant les niveaux d'immunité sérologiques les plus faibles étaient composés de femmes de moins de 25 ans ou n'ayant jamais été vaccinées ou vivant dans les districts d'Akre, de Bardarash ou de Shekhan du gouvernorat de Duhok. L'immunité antitétanique déterminée par la séroprévalence des taux d'antitoxine tétanique surpassait celle estimée à partir des antécédents de vaccination. Par conséquent, les marqueurs sérologiques devraient être utilisés à la place des antécédents vaccinaux pour déterminer le statut immunitaire.

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A possible explanation for the discrepancy between ELISA and neutralising antibodies to tetanus toxin

Cited by 24 publications

References 15 publications

Tetanus Immunity among Women Aged 15 to 39 Years in Cambodia: a National Population-Based Serosurvey, 2012

Tetanus Immunity among Women Aged 15 to 39 Years in Cambodia: a National Population-Based Serosurvey, 2012

Immunological Characteristics Associated with the Protective Efficacy of Antibodies to Ricin

Seroprevalence of tetanus antibodies among pregnant women in Duhok Governorate, Iraq

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