Tetanus immunoglobulin human 250units/1ml solution for injection pre-filled syringes

Abstract Tetanus remains an important global public health concern. Currently, the only recommended passive immunization therapy for tetanus prophylaxis is plasma-derived human tetanus immunoglobulin (HTIG), which faces a global supply shortage and can transmit infectious pathogens. Despite not being endorsed by WHO due to safety concerns, equine tetanus antitoxin remains widely used in some countries. We conducted a randomized, double-blind, phase 3 trial to evaluate siltartoxatug—a first-in-class recombinant monoclonal antibody—for tetanus postexposure prophylaxis. Participants ( n = 675) were randomized (2:1) to receive a single intramuscular injection of siltartoxatug 10 mg or HTIG 250 IU. The study met its primary outcome, with siltartoxatug demonstrating superiority to HTIG in the proportion of participants with an increase of anti-tetanus neutralizing antibody titers from baseline (ΔTiter) ≥ 0.01 IU ml − 1 (95.4% versus 53.2%; intergroup difference 42.3% (95% confidence interval, 35.5–49.1; P < 0.0001)). The safety profiles were comparable, with similar incidence of adverse events between the siltartoxatug (38.2%, 168 of 440) and HTIG (33.9%, 75 of 221) groups. These findings highlight siltartoxatug as an effective and safe option for passive immunization against tetanus. ClinicalTrials.gov registration: NCT05664750 .

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INTRODUCTION . Pharmaceutical production uses reference standards as an integral part of metrological support for analytical methods. A systematic literature analysis on standardisa­tion of human immunoglobulin preparations, particularly specific and special-purpose ones, will allow evaluating the metrological support in the Russian Federation and identifying new approaches to obtaining and using reference standards to assess specific potency. AIM . This study aimed to analyse published data on the range of reference standards used to evaluate potency of human immunoglobulins in the Russian Federation and abroad. DISCUSSION . PubMed, eLIBRARY.RU, and ConsultantPlus® legal research system showed that the list of international reference standards includes Rh 0 (D), hepatitis B, tetanus, staphylococcal and cytomegalovirus infections, rabies, and smallpox human immunoglobulins. No reference standard is available for human immunoglobulin against tick-borne encephalitis, since no specific human immunoglobulin is produced in the European Union. There is an absolute dependence on the import of international reference standards for assessing the potency of human hepatitis B, cytomegalovirus, and rabies immunoglobulins. Reference standards are typically obtained from ready-to-use batches of medicinal products and then stabilised, bottled under sterile conditions, and lyophilised. The Register of the State Pharmacopoeia of the Russian Federation includes reference standards for Rh 0 (D), anti-tetanus serum, and staphylococcal immunoglobulin. Unlike international reference standards, pharmacopoeial standards are produced as solutions, thus significantly reducing antibody stability. For pharmacopoeial reference standards, statistical uncertainty of the certified value is established in the Russian Federation; however, while certifying international reference standards, their certification is not obligatory. According to literature analysis, the key requirements for reference standards are stability and composition / properties similar to standardised preparations. Russian and foreign certification requirements of reference standards have certain differences. The number of Russian reference standards based on human immunoglobulin G is limited, since they are mostly obtained from horse blood serum. CONCLUSIONS . Russian pharmaceutical industry shows a deficit of national reference standards used for assessing specific potency of human immunoglobulins and donor plasma for their production. Thus, such reference standards should be released as lyophilisates and certified in international units, with an evaluation of statistical uncertainty of the antibody content.

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Background: Tetanus is a severe but vaccine-preventable disease controlled by tetanus toxoid (TT) immunization and tetanus immunoglobulin (TIG) therapy. Although maternal-neonatal tetanus has been eliminated in many regions, coverage gaps and sporadic cases persist in low-resource settings. As a longstanding component of global immunization and a key conjugate carrier platform, tetanus research remains essential despite advances in novel vaccine technologies. However, the global research landscape on tetanus vaccines and immunoglobulins remains unmapped. Objective: This study aimed to conduct a comprehensive bibliometric analysis of publications on TT and TIG from 2000 to 2025, to characterize research dynamics, leading contributors, and thematic evolution. Methods: We retrieved publications from the Web of Science Core Collection (SCI-Expanded) for 2000-2025 using relevant keywords ("tetanus vaccine*" OR "tetanus toxoid*" OR "tetanus immunoglobulin*" OR "tetanus immune globulin*" OR "tetanus antitoxin*"). Following screening, 2,949 English-language articles and reviews were included. Bibliometric analyses (publication trends, funding agencies, co-authorship, co-citation, and keyword co-occurrence) were performed using VOSviewer, CiteSpace, and the bibliometrix R package. Results: A total of 2,949 publications were analyzed. Annual output remained stable (mean ≈ 113.4), with citations peaking in 2021 (n=7,291). The USA led in volume (1,130 papers), while Switzerland achieved the highest impact (88.41 citations/article). The Centers for Disease Control and Prevention (CDC) and University of Oxford emerged as central hubs, with GlaxoSmithKline (GSK) illustrating the role of industry-academic partnerships. A strategic funding shift occurred around 2010: while the National Institutes of Health (NIH) drives foundational research, the Bill & Melinda Gates Foundation (BMGF) has become the engine for translational equity. Evolutionary trends show a shift from early cellular mechanisms toward maternal immunization coverage, implementation determinants in low- and middle-income countries (LMICs), and the expanding utility of tetanus toxoid (TT) as a conjugate vaccine carrier. Conclusion: Tetanus research has evolved into a dynamic model for modern vaccinology, bridging classical immunization and next-generation technology. Beyond maternal protection, the field is expanding toward conjugate platforms and recombinant biologics. Achieving global elimination requires aligning these biotechnological innovations with equitable implementation strategies in low-resource settings.

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Background: Luminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT). Methods: The MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzyme-linked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT. Results: We identified that an equimix of WHO international standards (i.e., 06/142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was < 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was < 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (> 0.75) with toxin neutralization assays for PT and DT was observed. Conclusion: The MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity.

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Background: The concentration of antigen-specific antibodies in serum is usually measured in international units/mL. Therefore, the actual concentration of virus-specific antibodies in sera is unknown. Objectives: The aim of the study was to determine conversion factors for concentrations of IgG against hepatitis B surface antigen (HBs), SARS-CoV-2 receptor binding domain (RBD) and nucleoprotein (NP) as well as tetanus toxin (Ttx) in serum and to compare antigen-specific IgG concentrations in serum samples. Methods: Absorption equivalence ELISAs were used to determine conversion factors for international units (IU) for anti-HBs, anti-SARS-CoV-2-RBD and NP and for anti-Ttx immunoglobulin G. The antigen-specific IgG concentrations in serum samples were then measured in units/mL and the ratio of IgG concentrations in the sera was determined using the conversion factors. Results: One IU of anti-HBs IgG corresponded to 24.4 BAU of anti-CoV-2 RBD IgG, 6.87 BAU of anti-CoV-2 NP and 14 mIU of anti-Ttx IgG. One BAU anti-SARS-CoV-2 NP-specific IgG is equivalent to 3.5 BAU SARS-CoV-2 RBD-specific IgG. Conversion of international units showed that median serum anti-Ttx-IgG concentrations were 50 times higher and anti-CoV-2-RBD-IgG concentrations were 390 times higher than median anti-HBs-IgG concentrations. In addition, after SARS-CoV-2 infection, the concentration of NP-specific IgG in serum was generally higher than that of RBD-specific IgG. Conclusions: The study provides conversion factors for serum concentrations of IgG against HBs, SARS-CoV-2 RBD and NP, as well as Ttx-IgG. This offers new insights into serum IgG concentrations and allows conclusions to be drawn about plasma cell pools.

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Background: Multiplex serological assays provide opportunities for seroprevalence studies and for evaluating antibodies post-vaccination. In this report, we describe the development and validation of a seven-plex bead-based assay for quantifying human immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), tetanus toxoid (TT), Haemophilus influenzae b (Hib), and hepatitis B (Hep B) using international reference standards. Methods: Existing international human reference sera standards are tailored for monoplex assays and, therefore, require characterization for multiplex assays. The reference standards for pertussis (06/142), diphtheria (10/262), tetanus (13/240), Hib (09/222), and Hep B (07/164) were characterized for their suitability in the assay. The purified antigens (PT, FHA, PRN, DT, TT, Hib, and Hep B) were coupled to spectrally unique magnetic carboxylated beads. The method was validated according to the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and International Council for Harmonization Multidisciplinary (ICH M10) guidelines. Validation parameters, such as precision, accuracy, dilution linearity, assay range, robustness, and solution stability, were assessed. Results: An equi-mix of an international reference standard for Hep B (07/164) and Hib (09/222) provided the best dynamic range for the seven-plex assay. Method validation was conducted using a panel of human serum samples that included samples from vaccinated healthy volunteers, non-vaccinated volunteers, negative controls, and international reference standards. Assay specificity using inhibition experiments demonstrated specificities of 98%, 95%, 93%, 98%, 97%, 97%, and 98% for DT, TT, FHA, PRN, PT, Hib, and Hep-B, respectively. Spike recoveries of 80%-120% were demonstrated in different matrices, including those of hemolytic and lipemic sera samples. The precision and accuracy were confirmed by evaluating a panel of human serum samples obtained from vaccinated individuals. The assay demonstrated coefficients of variation (CV) of ≤ 20% across all assays, regardless of run, day, or analyst. This method demonstrated strong agreement with conventional commercially available assays, highlighting the advantages of multiplexing over traditional enzyme-linked immunosorbent assays (ELISAs).

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Tetanus and botulism are neurotoxin-mediated diseases caused by Clostridium species but differ in their clinical manifestations and mechanisms of paralysis. Case: A 36-year-old woman presented with presented with rapidly progressive trismus, dysarthria, and facial paresthesia without an identifiable wound. Neuroimaging was normal. She had undergone laser eye surgery two days earlier and consumed home-canned food two weeks before admission. One month prior, her house had been flooded, and she recalled possible minor hand injuries sustained during post-flood cleaning. Given the typical rigidity and absence of focal neurological lesions, tetanus was suspected. Human tetanus immunoglobulin (HTIG, 500 IU intramuscularly) and intravenous metronidazole were administered, leading to complete resolution of symptoms within 24 hours. This case illustrates that even minimal or unnoticed injuries can serve as a portal of entry for Clostridium tetani . Non-wound tetanus should be considered in patients presenting with trismus and cranial symptoms, even when no wound is apparent.

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Introduction and Aim: Tetanus is a severe, potentially fatal disease caused by *Clostridium tetani*, a bacterium that produces a neurotoxin affecting the nervous system. This toxin impairs muscle contraction control, leading to characteristic symptoms such as trismus (lockjaw), muscle spasms, odynophagia, and high fever. Advanced cases may involve seizures and respiratory difficulties due to laryngeal muscle spasms. We aim to present a pediatric case of tetanus to highlight the clinical manifestations, treatment approach, and recovery process. Description of the Case: A thirteen-year-old Ukrainian boy with an unknown vaccination history was admitted to the pediatric infectious diseases unit with suspected tetanus. The disease presented with trismus, pain in the masticatory muscles, and discomfort in the tongue. Treatment involved the administration of human tetanus immunoglobulin, metronidazole, and penicillin. Over several days, the symptoms gradually subsided, and the patient experienced significant improvement. Conclusion: This case underscores the importance of timely diagnosis and comprehensive treatment in managing tetanus, particularly in patients with unknown vaccination histories. Early intervention, including immunoglobulin administration and appropriate antibiotics, can lead to a favorable outcome. The patient was discharged with medical recommendations and a follow-up plan, emphasizing the importance of vaccination in preventing this potentially life-threatening disease.

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