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Introduction and Objective: Vaccination is the most effective and reliable strategy for preventing the morbidity of tetanus. The aim of the study is to investigate the seroprevalence of antibodies to tetanus toxoid among healthy persons across all age groups to determine the level of vaccine-induced immunity in the population, and to identify which age group should be targeted for a booster dose., Material and Methods: A total of 2,842 serum samples collected between 2010 - 2019 from individuals aged from 1 month - 97 years were investigated. Anti-tetanus IgG antibody concentrations (IU/ml) were measured by an enzyme-linked immunosorbent assay. In addition, the avidity of antibodies was determined using an in-house ELISA., Results: The results showed that among the 2,842 individuals, 147 (5.2%) had anti-tetanus toxoid IgG antibody levels below 0.1 IU/ml and another 1,519 (53.4%) subjects showed only basic protection (0.1-1.0 IU/ml) and needed immediate booster. High levels of anti-tetanus toxoid IgG antibodies (>1.0 IU/ml) were found more often in young adults at the age 21-40 years (55.5%, GMT=1.15). Importantly, these antibodies also had the highest avidity. With age, the percentage of high positives decreased, as well as the geometric mean and avidity of antibodies, reaching the lowest level in subjects over 70 years of age (13.3%; GMT=0.19). Characteristically, a higher percentage of high positive results was observed in men (42.6%) than in women (34.3%)., Conclusions: The study showed adequate immunity levels to tetanus amongst the Polish population, especially in children, adolescents, and young adults. However, those from older age groups should receive booster doses of the vaccine.

Stage I of this study (NCT04142242) demonstrated the safety and immunogenicity of a booster dose of a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) and immune persistence 3 and 6-7 years after priming in older adults who received either quadrivalent meningococcal polysaccharide vaccine (MPSV4) or MenACYW-TT at ≥56 years of age. Stage II, reported here, assessed the antibody persistence after MenACYW-TT versus MPSV4 priming and the safety and immunogenicity of a booster dose of MenACYW-TT in older adults 5 years after primary vaccination with either MPSV4 or MenACYW-TT. A serum bactericidal assay (hSBA) was used to measure functional antibodies against each serogroup immediately before MenACYW-TT booster vaccination and on day (D) 30 post-booster. Safety was also assessed. Antibody persistence declined 5 years post-primary vaccination, with seroprotection (hSBA titer ≥1:8) rates trending higher in MenACYW-TT- versus MPSV4-primed participants. A robust immune response for all four serogroups was observed on D30 after the MenACYW-TT booster, with higher geometric mean titers and seroprotection rates in MenACYW-TT- versus MPSV4-primed participants. Safety outcomes were similar between the two groups. A single booster dose of MenACYW-TT was well tolerated and immunogenic in older adults, with a higher immune response observed in those primed with MenACYW-TT.

Vaccine safety and immunogenicity data in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children are important for decision-making in HIV and typhoid co-endemic countries. In an open-label study, we recruited Malawian HEU and HIV unexposed uninfected (HUU) infants aged 9 - 11 months. HEU participants were randomized to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) at 9 months, Vi-TT at 15 months, or Vi-TT at 9 and 15 months. HUU participants received Vi-TT at 9 and 15 months. Safety outcomes included solicited and unsolicited adverse events (AE) and serious AEs (SAEs) within 7 days, 28 days, and 6 months of vaccination, respectively. Serum was collected before and at day 28 after each vaccination to measure anti-Vi IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Cohort 1 (66 participants) enrollment began 02 December 2019, and follow-up was terminated before completion due to the COVID-19 pandemic. Cohort 2 (100 participants) enrollment began 25 March 2020. Solicited AEs were mostly mild, with no significant differences between HEU and HUU participants or one- and two-dose groups. All six SAEs were unrelated to vaccination. Anti-Vi geometric mean titers (GMT) increased significantly from 4.1 to 4.6 ELISA units (EU)/mL at baseline to 2572.0 - 4117.6 EU/mL on day 28 post-vaccination, and similarly between HEU and HUU participants for both one- and two-dose schedules. All participants seroconverted (>4-fold increase in GMT) by the final study visit. Our findings of comparable safety and immunogenicity of Vi-TT in HUU and HEU children support country introductions with single-dose Vi-TT in HIV-endemic countries.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis ( B. pertussis ) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p  = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p  < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

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., Competing Interests: Conflict of interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Tetanus is a non-communicable disease, preventable with vaccination. Despite the implemented vaccination strategy, a certain number of tetanus cases per year continue to occur. The aim of the study was to evaluate the seroprevalence of anti-tetanus antibodies in the Italian population by age, sex and geographical area., Methods: To determine the level of tetanus-specific antibodies, an immunoenzymatic assay was used., Results: A total of 3,821 serum samples were collected in the years 2019-20 from healthy subjects aged 6-90 years residing in 13 Italian regions. Overall, 85 % of the tested subjects resulted positive. The rate of subjects protected against tetanus showed a gradual decrease from the younger age groups to the older ones (6-12 years: 93.6 %, 13-24 years: 91.8 %, 25-39 years: 91.0 %, 40-64 years: 78.2 %, ≥ 65 years: 45.3 %); this is particularly evident in the Southern regions and Islands. Moreover, the prevalence of subjects with low protection (<0.1 IU/ml) was significantly higher in the ≥ 65 age group (10.3 %). Males and females' prevalence showed a significant difference only in the oldest age group (M: 60.8 %, F: 30.4 %). In general, a higher prevalence was observed for Northern (90.8 %) and Central regions (87.3 %) than Southern regions and Islands (80.0 %)., Conclusion: These data, compared with epidemiological ones which showed a high number of cases in the elderly, confirmed that the population with lower protection has a greater risk of contracting the disease, demonstrating the need for adequate immunization through both primary vaccination and boosters for all ages and both sexes, in order to provide lifelong protection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giovanni Gabutti reports a relationship with Emergent BioSolutions, the GSK group of companies, Merck Sharp & Dohme, Pfizer, Sanofi Pasteur Italy, Novavax, Viatris, Moderna and Seqirus that includes: board membership, consulting or advisory, and speaking and lecture fees. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap)., Methods: The Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4-65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of -10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components., Results: At Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported., Conclusions: Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated. EudraCT number: 2019-002706-46., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IA, MM, FP, NMM, LG reports a relationship with Serum Institute of India Pvt Ltd that includes: consulting or advisory. SP, PP, SS, SD, HS, HR, MG, SG, US reports a relationship with Serum Institute of India Pvt Ltd that includes: employment., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Idiopathic nephrotic syndrome is a childhood renal disease characterized by a damage of the glomerular filtration barrier leading to an intense leakage of proteins into the urine. This severe proteinuria causes a transient but strong reduction of serum IgG. Therefore, evaluation of vaccine competence by measuring serum levels of protective antibodies can be misleading in nephrotic syndrome, especially during the active phase of disease. To overcome this issue, in parallel to measuring serum antigen-specific IgG, we quantified by ELISPOT the number of antigen-specific memory B cells induced by previous immunization with tetanus and hepatitis B virus (HBV) in 11 steroid-sensitive nephrotic syndrome (SSNS) pediatric patients at onset before any immunosuppressive treatment (mean age 5.1±0.9 years). Five age-matched children with non-immunomediated nephro-urologic disorders were also enrolled as controls (mean age 6.9±2.3 years). Low total serum IgG levels (<520 mg/dl) were found in all the analyzed SSNS patients. In parallel, median levels of anti-tetanus and anti-HBV IgG were significantly reduced compared to controls [0.05 (0.03-0.16) vs. 0.45 (0.29-3.10) IU/ml and 0.0 (0.0-0.5) vs. 30.3 (5.5-400.8) mIU/ml, respectively; p = 0.02 for both], with serum IgG titers below protective threshold in 7/11 SSNS patients for tetanus and in 9/11 SSNS patients for HBV. In contrast, all SSNS patients had a competent B-cell response, showing an amount of total IgG-secreting B cells >1,000 counts/10 6 stimulated cells. The amount of anti-tetanus and anti-HBV IgG-secreting B cells was also comparable to that of controls ( p = 0.24, p = 0.32, respectively), with a frequency of memory anti-tetanus and anti-HBV IgG secreting B cells >0.1% of total IgG secreting B cells. In conclusion, SSNS children at disease onset pre-immunosuppressive therapy showed a competent immune and vaccine response against tetanus and HBV, which can be correctly evaluated by quantification of antigen-specific memory B cells rather than by measuring serum IgG levels. This approach allows early identification of the impairment of immune and vaccine competence, which may derive from protracted use of different immunosuppressive drugs during disease course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Colucci, Piano Mortari, Zotta, Corrente, Concato, Carsetti, Emma and Vivarelli.)

Tetanus toxoids (TT) commercially available for use in horses and livestock are commonly used to vaccinate elephants and rhinoceros that are in human care. Although recommendations for booster intervals have changed in human and horse protocols to reduce the risks associated with hyper-immunity (i.e. B-cell anergy and hypersensitivity reactions) these have generally not been adopted in zoo protocols. Additionally, there is no evidence to demonstrate commercial TT immunogenicity in rhinoceros. In this study, a preliminary analysis of rhinoceros antibody responses to TT was conducted, in addition to an exploration of the impact of various booster frequencies on antibody responses in elephant. Retrospective analysis of archived serum samples was conducted for 9 Asian elephants (Elephas maximus), 7 southern black (Diceros bicornis minor), one southern white (Ceratotherium simum simum), and two greater one-horned (Rhinoceros unicornis) rhinoceros. Pre-vaccination (baseline) samples and those following priming vaccination (rhinoceros only), annual and non-annual boosters were targeted. A commercially available competitive ELISA kit was used to quantify serum anti-TT antibodies. Average baseline and post-vaccination anti-tetanus antibody concentrations were greater in elephant (92 mg/L ± 42, n = 3, N = 3; 125 ± 76, n = 82, N = 9) than in rhinoceros (47 mg/L ± 39, n = 8, N = 8; 44 mg/L ± 37, n = 16, N = 7). Rhinoceros antibody concentrations did not differ markedly following vaccinations from their naturally acquired high pre-vaccination concentrations. Eight elephants demonstrated antibody maintenance for 3-5 years without a tetanus booster. Additionally, although five out of nine elephants developed local reactions consistent with delayed type IV hypersensitivity following some boosters, there was no association between high antibody concentrations and increased incidence of adverse reactions. In addition, no decrease in antibody concentrations was detected as a result of annual vaccination in elephants, though this does not entirely rule out potential for B-cell anergy., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of Clostridium tetani proteins, and the active component is present in variable and sometimes minor percentages of vaccine mass. Recombinant production of a genetically inactivated tetanus vaccine offers an opportunity to replace and improve the current tetanus vaccine. Previous studies showed the feasibility of engineering full-length tetanus toxin (TT) in Escherichia coli In the present study, full-length TT was engineered with eight individual amino acid mutations (8MTT) to inactivate catalysis, translocation, and host receptor-binding functions, retaining 99.4% amino acid identity to native tetanus toxin. 8MTT purified as a 150-kDa single-chain protein, which trypsin nicked to a 100-kDa heavy chain and 50-kDa light chain. The 8MTT was not toxic for outbred mice and was >50 million-fold less toxic than native TT. Relative to CITT, 8MTT vaccination elicited a strong immune response and showed good vaccine potency against TT challenge. The strength of the immune response to both vaccines varied among individual outbred mice. These data support 8MTT as a candidate vaccine against tetanus and a malleable candidate conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules to facilitate a rapid response to emerging microbial pathogens. IMPORTANCE Chemical inactivation is a clinically effective mechanism to detoxify protein toxins to produce vaccines against microbial infections and to serve as a platform for production of conjugate polysaccharide vaccines. This method is widely used for the production of protein toxin vaccines, including tetanus toxoid. However, chemical modification alters the protein structure with unknown effects on antigenicity. Here, a recombinant full-length tetanus toxin (TT) is engineered with 8 mutations (8MTT) that inactivate three toxin functions: catalysis, translocation, and receptor binding. 8MTT is nontoxic and elicits a potent immune response in outbred mice. 8MTT also represents a malleable platform for the production of conjugate vaccines, which can facilitate a rapid vaccine response against emerging microbial pathogens., (Copyright © 2020 Przedpelski et al.)

Background: To provide continuing protection, available meningococcal vaccines must provide long-term persistence of circulating functional antibodies against prevalent serogroups causing invasive meningococcal disease (IMD). This study assessed antibody persistence and safety of the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) and the meningococcal serogroup C vaccine conjugated to Corynebacterium diphtheriae CRM 197 protein (MenC-CRM) for up to 6 years after booster dosing in children., Methods: In the primary vaccination study, children were vaccinated at age 12 to 23 months. In the first extension study, children who completed the primary study received a booster dose 4 years later with the same primary vaccine. The current study assessed antibody persistence at 2 to 6 years postbooster against each of the 4 meningococcal serogroups using serum bactericidal assays using rabbit (rSBA) or human (hSBA) complement with antibody titer thresholds of ≥1:8 or ≥1:4, respectively, and geometric mean titers (GMTs). Safety evaluations during this period included serious adverse events (SAEs) related to vaccination and any event related to lack of vaccine efficacy., Results: A total of 184 subjects were enrolled (MenACWY-TT = 159; MenC-CRM = 25). For MenACWY-TT, the percentages of subjects with rSBA titers ≥1:8 ranged from 96.7% to 100% across serogroups at 2 years postbooster and 71.6% to 94.0% at 6 years postbooster; rSBA GMTs decreased from Year 2 to 4 and generally remained stable thereafter. The percentages of subjects in the MenACWY-TT group with hSBA titers ≥1:4 were 70.0% to 100% across serogroups at 2 years postbooster and 58.5% to 98.5% at 6 years postbooster. No lack of efficacy, SAEs, or vaccine-related adverse events were reported., Conclusions: The persistence of rSBA and hSBA antibodies was shown up to 6 years postbooster (10 years postprimary vaccination) with either MenACWY-TT or MenC-CRM, suggesting that this schedule may provide long-term protection against IMD. Clinicaltrials.gov: NCT01900899., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TV is a principal investigator for clinical trials sponsored by Pfizer, has received grants for participation in scientific conferences, and was paid for lectures. AF is an investigator for clinical trials sponsored by Pfizer. PL, CW, and JP are employees of Pfizer. FL is a former employee of Pfizer. MV is an employee of GlaxoSmithKline. MH was a consultant at Chiltern International for GlaxoSmithKline., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Aim of the Work: Thanks to the highly effective vaccine, tetanus became sporadic in high-income countries with well-established primary childhood immunization programs, but it is common in low-income countries. The migrants, leaving countries with poor immunization programs or where vaccinations have been interrupted, may represent a new risk group for tetanus in host countries. A seroprevalence study was conducted to estimate the immunological status against tetanus in young migrants without vaccination documentation., Methods: After a careful assessment by vaccination services of the Local Health Authority, all migrants recently arrived in Italy were included in the serosurvey. Titers of anti-tetanus toxoid were measured using a commercial ELISA kit. Subjects were stratified by age and by WHO region. Antibody titers <0.10 IU/ml were considered to be seronegative, between 0.10 and 1.00 IU/ml as intermediate protection, and >1.00 IU/ml high protection., Results: From January 2004 to December 2019, 2,326 blood samples were collected. Mean age was 13.9 years with no differences between WHO regions. The percentage of the subjects without protective antibodies was 22.3%, with an intermediate level was 45.2%, with high titer was 32.5%. Among migrant coming from African and Eastern Mediterranean WHO regions, the highest percentages of seronegative titers and, at the same time, the low percentages of high protective levels were found. Titers decreased with age., Conclusions: The significant proportion of seronegative migrants and the decrease of protective titers increasing age, confirm the importance of the evaluation of the immunological status to employ the appropriate vaccination strategy.

Streptococcus pneumoniae serotype 3 (ST3) is one of the main pneumococcal strains that can cause severe invasive diseases, but its current vaccines are relatively inefficient. To develop more effective ST3 vaccines, tetanus toxoid (TT) conjugates of the synthetic penta-, hexa-, hepta-, and octasaccharide analogs of ST3 capsular polysaccharide (CPS) were systematically studied. These conjugates, especially those of penta- and hexasaccharides, were demonstrated to induce extremely robust T cell-dependent immune responses in mouse. Various studies also revealed that the induced antibodies could recognize ST3 CPS and mediate in vitro opsonophagocytic killing of ST3 cells. It was proved ultimately that immunization with the hexasaccharide-TT conjugate could completely protect mice from ST3-caused infection and lung damage and significantly elongate mouse survival. It was proposed that this conjugate functions through the help of CD4+ T cells and via promoting Th cell differentiation into carbohydrate antigen-specific Th2 cells to establish humoral immunity. In conclusion, ST3 CPS hexasaccharide-TT was identified as a particularly promising ST3 vaccine candidate worthy of further investigation and development.

Background: We assessed immunogenicity, antibody persistence and safety of the meningococcal serogroups A, C, W and Y-tetanus toxoid (TT) conjugate vaccine (MenACWY-TT) in children primed as toddlers with MenC vaccine., Methods: This open, multicenter extension study enrolled children 84-95 months of age who had received one dose of the combined Haemophilus influenzae type b (Hib)-MenC-TT conjugate vaccine (HibMenC group) or Hib-TT and monovalent MenC (MCC)-CRM197 vaccines (Hib+MCC group) at 12-18 months of age, in the primary study. All participants received one dose of MenACWY-TT. We assessed immunogenicity against MenA, MenC, MenW and MenY at 1 month and 2 years postvaccination by serum bactericidal assay using baby rabbit complement (rSBA). Safety and reactogenicity were evaluated., Results: Six years post-MenC vaccination, <20% of children retained rSBA-MenC titers ≥1:8. At 1 month post-MenACWY-TT vaccination, vaccine response rates against all serogroups were high for both groups with ≥97.1% of children having rSBA ≥1:8. Two years postvaccination, ≥63.6% of children retained rSBA-MenA ≥1:8, and ≥87.9% for other serogroups. Geometric mean titers for all serogroups declined at 2 years post-MenACWY-TT vaccination, but remained ≥13 times higher than prevaccination levels. For both groups, pain (≤58.5%), redness (≤51.4%) and fatigue (≤27.0%) were the most frequently reported adverse events. No serious adverse events were reported., Conclusions: One dose of MenACWY-TT boosts protection against MenC in primed children, is safe and extends protection against MenA, MenW and MenY. Immunogenicity and safety were comparable in infants vaccinated with conjugated vaccine (HibMenC-TT) or the separate vaccines (Hib-TT and MCC-CRM197).

Submicroscopic Plasmodium infections in pregnancy are common in endemic areas, and it is important to understand the impact of these low-level infections. Asymptomatic, chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiological conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations. These alterations of the immune system could compromise the response to routine vaccination. This study aimed to evaluate the effect of submicroscopic plasmodial infection with P. falciparum and P. vivax during pregnancy on the immune response to the tetanus toxoid vaccine in Colombian women. Expression of different cytokines and mediators of immune regulation and levels of anti-tetanus toxoid (TT) immunoglobulin (Ig)G were quantified in pregnant women with and without submicroscopic plasmodial infection. The anti-TT IgG levels were significantly lower in the infected group compared with the uninfected group. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF) and forkhead box protein 3 (FoxP3) was significantly higher in the infected group, while the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and transforming growth factor (TGF)-β was lower in the group of infected. In conclusion, submicroscopic Plasmodium infection altered the development of the immune response to the TT vaccine in Colombian pregnant women. The impact of Plasmodium infections on the immune regulatory pathways warrants further exploration., (© 2018 British Society for Immunology.)

Background : This exploratory study aimed to assess the immunogenicity and safety of 1 and 2 doses of meningococcal serogroups A and C tetanus toxoid-conjugate vaccine (MenAC-TT) in toddles. Methods : Healthy participants aged 12-23 months were randomized into two groups to receive 1 or 2 doses of the tested vaccine. The interval was 28 days between two doses. Blood samples were collected at day 0 before the immunization and day 28 post-each dose. Safety observation was conducted during 28 days after each vaccination. Serious adverse event (SAE) was conducted throughout 6 month observation period. Results : Overall 301 toddles were vaccinated. Twenty-eight days post full-course vaccination, ≥97.20% toddles had titers ≥1:8 and ≥81.48% had titers ≥1:128 for MenA and MenC in the two schedules groups. There were no significant differences between the two schedule groups for each titer thresholds and serogroups. Up to month 12 post the first dose, titers ≥1:8 and 1:128 were declined to 71.32-80.83% and 26.67-57.85% for each meningococcal serogroups. Most adverse reactions (ARs) were mild or moderate, and the incidence of grade 3 ARs was below 3.33%. The incidence of redness was significantly higher in the two doses group than that in the one dose group, in terms of grade 1 and grade 2 were higher. No SAEs were considered causally related to vaccination. Conclusion : The MenAC-TT showed similarly safety and immunogenicity profile in toddles with two schedules. It will be more important to provide the data for formulating appropriate immunization strategies in different age groups in China.

Introduction: Tetanus infection associated with men who had male circumcision has been reported in East Africa, suggesting a need for tetanus toxoid-containing vaccines (TTCV)., Objective: To determine the prevalence of tetanus toxoid antibodies following vaccination among men seeking circumcision., Methods: We enrolled 620 consenting men who completed a questionnaire and received TTCV at enrollment (day 0) prior to circumcision on day 28. Blood samples were obtained at day 0 from all enrollees and on days 14, 28 and 42 from a random sample of 237 participants. Tetanus toxoid (TT) IgG antibody levels were assayed using EUROIMMUN. Analyses included prevalence of TT antibodies at enrollment and used a mixed effects model to determine the immunological response., Results: Mean age was 21.4 years, 65.2% had knowledge of tetanus, 56.6% knew how tetanus was contracted, 22.8% reported ever receipt of TTCV, and 16.8% had current/recently healed wounds. Insufficient tetanus immunity was 57.1% at enrollment, 7.2% at day 14, 3.8% at day 28, and 0% at day 42. Antibody concentration was 0.44IU/ml (CI 0.35-0.53) on day 0, 3.86IU/ml (CI 3.60-4.11) on day 14, 4.05IU/ml (CI 3.81-4.29) on day 28, and 4.48IU/ml (CI 4.28-4.68) on day 42. TT antibodies increased by 0.24IU/ml (CI 0.23, 0.26) between days 0 and 14 and by 0.023IU/ml (CI 0.015, 0.031) between days 14 and 42 days. Immunological response was poorer in HIV-infected clients and men aged 35+ years., Conclusion: Insufficient immunity was common prior to TTCV, and a protective immunological response was achieved by day 14. Circumcision may safely be provided 14 days after vaccination in HIV-uninfected men aged less than 35 years., Competing Interests: The authors have declared that no competing interests exist.

Background: Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce., Objective: To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL)., Methodology: Thirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme. Blood samples were collected immediately before and after vaccine. Lymphocyte immunophenotyping was performed by flow cytometry; tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with tetanus toxoid and Bordetella pertussis and supernatants were assessed for cytokines by xMAP., Results: Mean age of HIV and CONTROL groups were 17.9 e 17.1 years, respectively. Pain at injection site was more intense in CONTROL group. HIV group had similar increase in tetanus antibodies at 28 days (geometric mean concentration, GMC, 15.6; 95% CI, 7.52-32.4) than CONTROL group (GMC, 23.1; 95% CI, 15.0-35.5), but lower diphtheria antibodies at 28 days (GMC, 2.3; 95% CI, 0.88-6.19) than CONTROL group (GMC, 16.4; 95% CI, 10.3-26.2); for pertussis, the percentage of individuals who seroconverted was lower in HIV than CONTROL group (HIV, 62.1% versus CONTROL, 100%; p = .002). Both groups built a cellular immune response to tetanus, with a Th2 (IL-4, IL-5 and IL-13) and Th1 (IFN-γ) response, with lower cytokine levels in HIV than in CONTROL group. Especially for pertussis, cellular and humoral responses were less intense in HIV adolescents, with a lower Th1 and Th17 profile and higher IL-10 levels. HIV-infected adolescents on viral suppression showed an enhanced immune response to all the three vaccine antigens, although still at lower levels if compared to CONTROL group., Conclusions: Both groups tolerated well and built an immune response after Tdap. However, HIV-infected adolescents would probably benefit from more frequent booster doses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Our previous study suggested newborns have competent immune systems with the potential to respond to foreign antigens and vaccines. In this study, we examined infant immune responses to tetanus toxoid (TT) vaccination in the presence of maternal antibody to TT., Methods: We examined changes in plasma levels of tetanus toxoid-specific IgG1 (anti-TT IgG1) in a total of eight infant rhesus macaques from birth through 6 months of age using a commercial Monkey Anti-TT IgG1 ELISA kit., Results: A significant correlation between anti-TT IgG1 levels in vaccinated dams and their paired newborn infants was detected in control (non-vaccinated) infants as previously reported. Maternal anti-TT IgG1 levels declined rapidly within 1 month of birth in non-vaccinated infants (n=4). In four infants vaccinated with TT at birth, we found two had rapid and robust antibody responses to vaccination. Interestingly, the other two first showed declining TT antibody levels for 2 weeks followed by increasing levels without additional vaccine boosts, indicating all four had good antibody responses to primary TT vaccination at birth, despite the presence of high levels of maternal antibodies to TT in all four infants., Conclusions: Our data indicate that newborn macaques have competent immune systems that are capable of generating their own primary antibody responses to vaccination, at least to tetanus antigens. Maternal antibodies thus do not significantly impair antibody response to the vaccination, even when received on the day of birth in infant rhesus macaques., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Immune competence can be tested by challenging organisms with a set of infectious agents. However, disease control requirements impose restrictions on the infliction of infections upon domestic pigs. Alternatively, vaccinations induce detectable immune responses that reflect immune competence. Here, we tested this approach with tetanus toxoid (TT) in young domestic pigs. To optimize the vaccination protocol, we immunized the pigs with a commercial TT vaccine at the age of 21 or 35 days. Booster immunizations were performed either 14 or 21 days later. TT-specific antibodies in plasma as well as lymphoproliferative responses were determined both 7 and 14 days after booster immunization using ELISA and lymphocyte transformation tests, respectively. In addition, general IgG and IgM plasma concentrations and mitogen-induced proliferation were measured. The highest TT-specific antibody responses were detected when blood samples were collected 1 week after a booster immunization conducted 21 days after primary immunization. The pigs' age at primary immunization did not have a significant influence on TT-specific antibody responses. Similarly, the TT-specific proliferative responses were highest when blood samples were collected 1 week after booster immunization, while age and time of primary and booster immunization were irrelevant in our setup. While general IgG and IgM plasma levels were highly age dependent, there were no significant age effects for TT-specific immune responses. In addition, mitogen-induced proliferation was independent of immunization as well as blood sampling protocols. In summary, our model of TT vaccination provides an interesting approach for the assessment of immune competence in young pigs. The detected vaccination effects were not biased by age, even though our data were acquired from immune systems that were under development during our tests.

We report the development of a novel flow cytometry-based Ig capture assay (ICA) for the identification and sorting of individual Ab-secreting cells based on their Ag reactivity. The ICA represents a fast and versatile tool for single-cell sorting of peripheral plasmablasts, streamlining subsequent Ab analysis, and cloning. We demonstrate the utility of the assay by isolating Ag-reactive plasmablasts from cryopreserved PBMC obtained from volunteers vaccinated with a recombinant HIV envelope protein. To show the specificity of the ICA, we produced Ag-specific Abs from these cells and subsequently verified their Ag reactivity via ELISA. Furthermore, we used the ICA to track Ag-specific plasmablast responses in HIV-vaccine recipients over a period of 42 d and performed a head-to-head comparison with a conventional B cell ELISpot. Results were highly comparable, highlighting that this assay is a viable alternative for monitoring Ag-specific plasmablast responses at early time points after infection or vaccination. The ICA provides important added benefits in that phenotypic information can be obtained from the identified Ag-specific cells that can then be captured for downstream applications such as B cell sequencing and/or Ab cloning. We envisage the ICA as being a useful tool in Ab repertoire analysis for future clinical trials., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Background: Postnatal exposure to perfluorinated alkylate substances (PFASs) is associated with lower serum concentrations of specific antibodies against certain childhood vaccines at 7 y., Objectives: We prospectively followed a Faroese birth cohort to determine these associations at 13 y., Methods: In 516 subjects (79% of eligible cohort members) who were 13 years old, serum concentrations of PFASs and of antibodies against diphtheria and tetanus were measured and were compared with data from the previous examination at 7 y. Multiple regression analyses and structural equation models were applied to determine the association between postnatal PFAS exposures and antibody concentrations., Results: Serum concentrations of PFASs and antibodies generally declined from 7 y to 13 y. However, 68 subjects had visited the emergency room and had likely received a vaccination booster, and a total of 202 children showed higher vaccine antibody concentrations at 13 y than at 7 y. Therefore, separate analyses were conducted after exclusion of these two subgroups. Diphtheria antibody concentrations decreased at elevated PFAS concentrations at 13 y and 7 y; the associations were statistically significant for perfluorodecanoate (PFDA) at 7 y and for perfluorooctanoate (PFOA) at 13 y, both suggesting a decrease by ∼25% for each doubling of exposure. Structural equation models showed that a doubling in PFAS exposure at 7 y was associated with losses in diphtheria antibody concentrations at 13 y of 10–30% for the five PFASs. Few associations were observed for anti-tetanus concentrations., Conclusions: These results are in accord with previous findings of PFAS immunotoxicity at current exposure levels. https://doi.org/10.1289/EHP275.

The aim of the present research is to verify the immune status against tetanus in students and workers exposed to risk and to ascertain whether a decennial booster is necessary. Antibodies against tetanus were measured in 1433 workers and students of Padua University (Italy). The enrolment criterion was the ability to provide a booklet of vaccinations released by a public health office. The influence of age, gender, the number of vaccine doses, and the interval since the last dose was determined. Ten years after the last dose, the majority of subjects (95·0%) displayed an antibody titre above the protective level (⩾0·10 IU/ml), and half of these (49·1%) had a long-term protective level (⩾1·0 IU/ml). According to our data, titre depends on both the number of vaccine doses and the interval since the last dose (P < 0·0001). Five vaccine doses and an interval of at least 10 years since the last dose are predictive of a long-term protective titre in absence of a booster (1·97 IU/ml). These data suggest that when primary series are completed, a decennial booster is unnecessary for up to 20 years. Furthermore, we recommend measuring the antibody level before a new booster is given to prevent problems related to over-immunisation.

A dot immunoassay for simultaneous semiquantitative detection of IgG against tetanus toxoid (Ttx) and diphtheria toxoid (Dtx) and qualitative detection of anti-Bordetella pertussis IgGs in human blood serum using carbon nanoparticles functionalized with streptococcal protein G was developed. Inactivated B. pertussis cells in suspension form were used as an antigen in the immunoassay. Pertussis, tetanus, and diphtheria antigens were separately spotted onto nitrocellulose strips, and then the immunostrips were successively incubated with blood sera and a suspension of carbon nanoparticles. The immunostrips were then scanned with a flatbed scanner, and the images obtained were processed with ImageJ. One hundred fifty-five venous blood serum samples from children vaccinated with diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine were tested in comparison with a conventional ELISA and agglutination test. The total time required for analysis of 32 serum samples was less than 3 h. Comparison between the results of the dot immunoassay and the corresponding ELISA/agglutination test revealed a high level of agreement (Cohen's kappa between 0.765 and 0.813). The lower limit of quantification was 0.06 IU/ml for anti-Ttx and anti-Dtx. The intra-assay coefficients of variation were less than 15% for anti-Ttx and anti-Dtx and less than 10% for anti-pertussis. The diagnostic sensitivity of detection of the antibody protection level was 93.5% for anti-Ttx [95% confidence interval (CI) 83.5-97.9%], 92.4% for anti-Dtx (95% CI 80.9297.5%), and 90.2% for anti-pertussis (95% CI 75.9-96.8%). The diagnostic specificity was 90.9% for anti-Ttx (95% CI 57.1-99.5%), 85% for anti-Dtx (95% CI 61.1-96.0%), and 89.3% for anti-pertussis (95%CI 80.8-94.5%). The dot immunoassay developed does not require expensive reading equipment, and allows detection of antibodies against three antigens in a single analysis. The immunostrips can be stored for a long time without changes in the coloration of the spots. Graphical Abstract The assay procedure. BC Bordetella pertussis cell suspension, CNP carbon nanoparticle, Dtx diphtheria toxoid, Ttx tetanus toxoid.

We have developed recombinant fragment C based rapid point of care dipstick devices to assess tetanus immunization status using plasma or whole blood. The devices demonstrated specificity of 0.90 and sensitivity of 0.90 (whole blood)/0.94 (plasma) at field sites in Bangladesh and The Gambia when compared to a commercial ELISA with the immune cut-off titer set as ≥0.1IU/mL., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual's ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT., Methods: Adults were recruited from Kisumu Polytechnic College in Western Kenya. At enrollment, participants were screened for schistosomiasis and soil transmitted helminths (STHs) and assigned to groups based on helminth status. The vaccines were then administered and helminth infections treated a week after the first hepatitis B boost. Over an 8 month period, 3 blood specimens were obtained for the evaluation of humoral and cytokine responses to the vaccine antigens and for immunophenotyping., Results: 146 individuals were available for final analysis and 26% were S. mansoni positive (Sm+). Schistosomiasis did not impede the generation of initial minimum protective antibody levels to either hepatitis B or TT vaccines. However, median hepatitis B surface antibody levels were significantly lower in the Sm+ group after the first boost and remained lower, but not significantly lower, following praziquantel (PZQ) treatment and final boost. In addition, 8 months following TT boost and 7 months following PZQ treatment, Sm+ individuals were more likely to have anti-TT antibody levels fall below levels considered optimal for long term protection. IL-5 levels in response to in vitro TT stimulation of whole blood were significantly higher in the Sm+ group at the 8 month time period as well., Conclusions: Individuals with schistosomiasis at the start the immunizations were capable of responding appropriately to the vaccines as measured by antibody responses. However, they may be at risk of a more rapid decline in antibody levels over time, suggesting that treating schistosome infections with praziquantel before immunizations could be beneficial. The timing of the treatment as well as its full impact on the maintenance of antibodies against vaccine antigens remains to be elucidated., Competing Interests: The authors have declared that no competing interests exist.

Background: Use of a polysaccharide vaccine challenge to demonstrate immunologic memory after priming with capsular group C meningococcal conjugate vaccines (MenCC) risks induction of immunologic hyporesponsiveness. For this reason, MenCC vaccines are now used as probes of immunologic memory, however, no studies have demonstrated their ability to distinguish primed from unprimed children., Methods: This study was part of a randomised controlled trial investigating the immunogenicity of a booster dose of the combined Haemophilus influenzae type b and MenC-tetanus toxoid vaccine (Hib-MenC-TT) in infants receiving reduced dose MenCC vaccine priming schedules (one MenC-CRM/MenC-TT or two MenC-CRM vaccine doses) compared with an unprimed group. Antibody kinetics were studied in a subset of 269 children by measuring changes in the MenC serum bactericidal antibody, using rabbit complement, (MenC rSBA) titres and MenC specific IgG memory B-cells before and at 6 and 28days following the 12month booster vaccination., Results: At 6days after the 12monthMenCC vaccine, the rise in MenC rSBA titres and MenC specific IgG memory B-cells of the primed groups were significantly higher than the infant MenCC naïve group. Participants primed with one MenC-TT dose had the highest increase in MenC rSBA titres compared with all other groups. The MenC rSBA titres at the 28th compared with the 6th day after boosting was significantly higher in those primed with a single MenC-TT/MenC-CRM vaccine in infancy compared with those who were not primed or who were primed with two doses of the MenC-CRM vaccine., Conclusion: Immunologic memory can be demonstrated by a MenCC booster vaccination but is affected by the type and number of MenCC doses used for infant priming. The MenC rSBA responses can be used to demonstrate successful immunologic priming., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Due to waning immunity, infant vaccination with meningococcal serogroup C conjugated (MenCC) vaccines is insufficient to maintain long-term individual protection. Adolescent booster vaccination is thought to offer direct protection against invasive meningococcal disease (IMD) but also to reduce meningococcal carriage and transmission and in this way establish herd protection in the population. Previously, we studied antibody levels after adolescent MenCC booster vaccination. In the present study, the adolescent vaccinees were revisited after three years to determine antibody persistence and to predict long-term protection., Methods: Meningococcal serogroup C tetanus toxoid conjugated (MenC-TT) vaccine was administered to 10-, 12- and 15-year old participants who had been primed nine years earlier with a single dose of MenC-TT vaccine. Blood samples were collected before, 1month, 1year and 3years after the adolescent booster vaccination. Functional antibody levels were measured with serum bactericidal assay using rabbit complement (rSBA). Meningococcal serogroup C polysaccharide and tetanus toxoid specific antibody levels were measured using fluorescent-bead-based multiplex immunoassay. Long-term protection was estimated using longitudinal multilevel antibody decay modeling., Results: Of the original 268 participants, 201 (75%) were revisited after 3years. All participants still had an rSBA titer above the protective threshold of ⩾8 and 98% ⩾128. The 15-year-olds showed the highest antibody titers. Using a bi-exponential decay model, the median time to fall below the protection threshold (rSBA titer <8) was 16.3years, 45.9years and around 270years following the booster for the 10-, 12- and 15-year-olds, respectively., Conclusions: After a first steep decline in antibody levels in the first year after the booster, antibody levels slowly declined between one and three years post-booster. A routine MenC-TT booster vaccination for adolescents in the Netherlands will likely provide long-term individual protection and potentially reduce the risk of resurgence of MenC disease in the general population., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children.Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule.Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection.Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies.The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The decrease in antibody titers occurring over time is a significant factor in vaccination program planning.Tetanus antibody concentrations were found to be high, but responses to the diphtheria and tetanus components were divergent. The percentage of children protected against diphtheria was significantly lower than protected against tetanus., Competing Interests: All the authors declare no conflicts of interests.

Reasons for Performing Study: Recommendations for prophylactic vaccination against tetanus in horses vary greatly between countries and have scarce scientific support in the peer-reviewed literature. In human medicine, recommended booster vaccination intervals are also very variable, but are considerably longer than for horses. More information is needed about the duration of immunity induced by modern vaccines., Objectives: To investigate if the duration of antibody titres previously determined to be protective against tetanus differ from what is indicated by recommended vaccination intervals for horses., Study Design: Prospective seroconversion study., Methods: Thirty-four horses were enrolled for basic immunisation with an ISCOM Matrix-combination vaccine (Equilis Prequenza Te). Horses received the first vaccination at age 5-11 months, and the second dose 4 weeks later. A third vaccine dose was given 15-17 months after the second dose. Serum tetanus antibody titres were analysed by toxin-binding enzyme-linked immunosorbent assay 2 weeks as well as 14-16 months after the second dose. After the third vaccine dose, titres were checked once yearly for 3 years. Results were described by age and level of antibody titre at first sampling., Results: Two weeks after the second dose, all horses (34/34) had antibody levels that exceeded the limit of detection, 0.04 iu/ml. After 16 months the levels were above 0.04 iu/ml in 28/33 horses, the remaining 5 horses potentially had suboptimal protection against tetanus. After the third vaccine dose antibody levels remained above 0.04 iu/ml in 25/26 horses for 1 year, 16/16 horses for 2 years, and 8/8 horses for 3 years., Conclusions: Horses that undergo basic immunisation with 3 doses of vaccine after age 5 months are likely to have serum antibody titres consistent with protection against tetanus for more than 3 years. Current guidelines for tetanus prophylaxis should be revised., (© 2015 EVJ Ltd.)

We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT00891176.)., (Copyright © 2016 Tejedor et al.)

The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7-9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy.

Vi polysaccharide typhoid vaccines cannot be used in children <2 years owing to poor immunogenic and T cell independent properties. Conjugate vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children <2 years. We evaluated efficacy and safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.

Background: Tetanus neurotoxin (TeNT) is composed of a light (LC) and heavy chain (HC) polypeptides, released by anaerobic bacterium Clostridium tetani and can cause fatal life-threatening infectious disease. Toxin HC and LC modules represents receptor binding and zinc metalloprotease activity, respectively. The passive administration of animal-derived antibodies against tetanus toxin has been considered as the mainstay therapy for years. However, this treatment is associated with several adverse effects due to the presence of anti-isotype antibodies., Objective: In the present study, we have produced the fully human single chain antibody fragments (HuScFv) from two human antibody phage display libraries., Material and Methods: Twenty-four different HuscFvs were isolated from two anti TeNT immune libraries. Our produced human ScFv (HuScFv) were converted to IgG platform and analyzed regarding their specific reactivity to TeNT., Results: All of the selected scFvs have the same VL but different VH. Three HuscFvs from the first library (TTX15, 51, 75) and two HuscFvs from the second library (TTX16, 20) were chosen to convert to IgG1 using pOptiVEC and pcDNA3.3 systems. Production of IgG1 from transfected DG44 and binding capacity of them to tetanus toxin and toxoid were measured by ELISA. ELISA results showed no detectable production of TTX16 and TTX20 IgG1. Although, TTX51 and TTX75 were converted and produced as IgG1, no reactivity to tetanus toxin and toxoid was observed. However, TTX15 was successfully produced as whole IgG1 platform with reactivity to both tetanus toxin and toxoid. The latter would be an appropriate replacement for conventional polyclonal antibodies if would meet the further characterization including specificity determination, affinity measurement and toxin neutralizing assays., Conclusion: Our results demonstrated production of functional IgG1 derived from TTX15 scFv and might be an appropriate replacement for polyclonal Tetabulin but it needs further characterization.

Introduction: In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM., Methods: Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age., Results: Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold-change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold-differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54-0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM-conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher., Conclusions: Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM-conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC)., Methods: This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naïve toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit., Results: The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers ≥1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations ≥0.15 μg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported., Conclusions: Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations ≥0.15 μg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers ≥1:8 was low (≤25%), suggesting that a MenC booster dose may be warranted before adolescence.

Background: Cancer survival rates and longevity of patients after therapy have significantly improved during the last decades. Thus durable protection against infections should be provided. The aim of the study was to compare the levels of vaccine-derived antibodies in children with cancer compared to those of healthy children and to investigate how therapy influences the levels of specific antibodies., Procedure: A group of 40 children, diagnosed with acute lymphoblastic leukemia (ALL) or solid tumor (ST), followed in Poznan University of Medical Sciences Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, were recruited for evaluation of humoral immunity. Antibody levels were checked before treatment and 3, 6, and 12 months after treatment., Results: In patients with ALL or ST, levels of IgG against tetanus and diphtheria were significantly lower than in the control group. Among ALL patients, 9% remained negative for tetanus and diphtheria antibodies 12 months after therapy. Among patients with ST 3 months after chemotherapy, there were no protective antibodies in 12% against tetanus, and in 18% against diphtheria. All patients reconstituted immunity 6 and 12 months after therapy., Conclusions: Our data show that a considerable number of cancer patients lose immunity against diphtheria and tetanus after therapy. Compared to ST, patients with ALL lose protective antibody levels more often. Patients with ST reconstituted antibodies after the treatment cessation, while levels in ALL patients remained low., (© 2015 Wiley Periodicals, Inc.)

Background: In 2010, mass vaccination with a then-new meningococcal A polysaccharide-tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction., Methods: Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ≥0.1 IU/mL (indicating short-term protection) and ≥1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models., Results: Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre-PsA-TT, significantly higher GMCs in all age-sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6-36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7-43.3; P < .0001) pre- and postvaccination., Conclusions: Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12-23 months of age., Methods: Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A-specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay., Results: The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P < .0001). Group A-specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P < .0001). One week following revaccination, those given 2 doses of PsA-TT had the greatest IgG1 and IgG2 GMCs of 125.23 µg/mL and 36.12 µg/mL, respectively (P = .0008), and demonstrated a significant increase in IgG1:IgG2 mean ratio, indicative of the T-cell-dependent response associated with conjugate vaccines., Conclusions: Vaccination of African children aged 12-24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell-independent immune response commonly associated with polysaccharide antigens., Clinical Trials Registration: SRCTN78147026., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.)

The immunogenicity of Bacillus anthracis capsule (poly-γ-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >10(3) were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 10(3). An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 10(4) following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT-induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) mechanisms, a strong immune response against the carrier protein could suppress the immune response to PS after coadministration of free carrier protein with the conjugate vaccine. However, it was not clear whether suppressing or enhancing the protein-specific immunogenicity could improve the PS-specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation, extensive PEGylation and oligomerization were used to regulate the immunogenicity of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-TT. In contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6-fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation through mild suppression of the TT-specific immunogenicity. The PS-specific immunogenicity of PS-TT was decreased through significant suppression or enhancement of the TT-specific immunogenicity. Thus, our study contributes to understand the CIES mechanisms and improve the PS-specific immunogenicity of a meningococcal PS conjugate vaccine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Meningococcal disease is a fatal illness of sudden onset caused by Neisseria meningitides. Meningococcal capsular polysaccharide (CPS) is a major virulence factor that generally does not induce immunological memory. Conjugation with a carrier protein can significantly increase the immunogenicity of CPS and induce immunological memory. However, it is highly desired to optimize the CPS-specific immunogenicity of the conjugate vaccine. Although adjuvant has been widely used to improve the immunogenicity of antigens, co-administration and conjugation of adjuvant with the conjugate vaccine has rarely been investigated. As a stimulator of humoral and cellular immunity, β-glucan can activate macrophages and trigger intracellular processes to secrete cytokines initiating inflammatory reactions. In the present study, a conjugate vaccine (CPS-TT) was generated by conjugation of tetanus toxoid (TT) with meningococcal group Y CPS. CPS-TT was further conjugated with β-glucan to generate CPS-TT-G. Immunization with CPS-TT-G led to an 8.2-fold increase in the CPS-specific IgG titers as compared with CPS-TT. Presumably, conjugation of β-glucan ensured the two components to simultaneously reach the antigen presenting cells and stimulate the immune response. In contrast, co-administration of β-glucan suppressed the CPS-specific immunogenicity of CPS-TT. Thus, conjugation of β-glucan is an effective strategy to markedly improve the CPS-specific immunogenicity of the conjugate vaccine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The use of different limbs for the administration of sequential doses of an intradermal rabies vaccine was shown to result in reduced vaccine immunogenicity. We aimed to assess whether this phenomenon also occurs with routine infant vaccines., Methods: In this open-label, randomised, controlled study, eligible healthy infants 6-12 weeks of age recruited through five clinical trials units (four in the UK and one in Malta) were randomly assigned in a 1:1 ratio to two vaccination groups: consistent limb or alternating limb. Infants in the consistent limb group received the diphtheria-tetanus-acellular pertussis-inactived polio-Haemophilus influenzae type b combined vaccine (DTaP-IPV-Hib) at 2, 3, and 4 months of age, and the pneumococcal conjugate vaccine (PCV13) at 2, 4, and 12 months, all administered to the right leg. Infants in the alternating limb group received DTaP-IPV-Hib in the left leg at 2 months and in the right leg at 3 and 4 months; and PCV13 in the left leg at 2 months, in the right leg at 4 months, and in the left arm at 12 months. All infants in both groups received the combined H influenzae type b and capsular group C Neisseria meningitidis tetanus toxoid conjugate vaccine (Hib-MenC-TT), administered in the left leg at 12 months. Randomisation was achieved by randomly generated codes, with permuted block size of 30, and was stratified by study site. Group allocation was not masked from study staff and parents of participants after enrolment, but group allocation was masked from laboratory staff assessing blood samples. The current study was a prespecified secondary objective of a parent phase 4 trial that assessed the induction of immunity following varying schedules of vaccination with glyco-conjugate capsular group C Neisseria meningitidis (Men C) vaccines in infancy. The objective of the current study was to compare the immunogenicity and reactogenicity of vaccines delivered in either consistent or alternating limbs. Immunogenicity was assessed by comparing serum IgG geometric mean concentrations at 5, 12, 13, and 24 months, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01129518., Findings: Between July 5, 2010, and Aug 1, 2013, we enrolled 509 infants and randomly allocated them to the consistent limb group (n=254) or the alternating limb group (n=255). Anti-H influenzae type b anti-polyribosylribitol phosphate IgG geometric mean concentrations were lower in the consistent limb group than in the alternating limb group at 5 months (consistent limb 0·41 μg/mL [95% CI 0·31-0·54] vs alternating limb 0·61 μg/mL [0·45-0·82]; p=0·0268) and at 12 months (0·35 μg/mL [0·28-0·43] vs 0·50 μg/mL [0·40-0·62]; p=0·0136). Anti-tetanus toxoid antibody IgG geometric mean concentrations were lower in the consistent limb group (1·63 IU/mL [95% CI 1·40-1·90]) than in the alternating limb group (2·30 IU/mL [1·97-2·68]) at 13 months (p=0·0008) and at 24 months (0·44 IU/mL [0·37-0·52] vs 0·61 IU/mL [0·51-0·73]; p=0·0074). Anti-pneumococcal IgG geometric mean concentrations were similar between both groups at all timepoints. The proportions of participants who had adverse events did not differ between the two groups., Interpretation: Use of different (alternating) limbs for sequential doses of routine infant vaccines does not reduce, and might enhance, immunogenicity. The underlying mechanism for this finding warrants further research., Funding: NIHR Oxford Biomedical Research Centre and GlaxoSmithKline Biologicals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Tétanos Quick Stick® (TQS) is a test for tetanus immunity screening for wounded patients in emergency departments (EDs), but represents additional costs compared with a medical interview on vaccination history. The study objective was to assess the effectiveness and cost of the TQS in French EDs., Methods: We performed a model-based analysis that simulates screening of tetanus immunity and risk of tetanus based on prophylaxis administration. Strategies compared were: i) diagnosis of tetanus immunity by "TQS"; ii) "Medical Interview" (current practice). The study population was 1,658,000 French adults seeking ED care for a wound in 2012. Model parameters were estimated based on French national surveillance data, and published literature. Outcome measures were number of tetanus cases, life years gained and costs (2012 €) from a societal perspective., Results: Use of TQS had negligible impact on health outcomes (0.02 tetanus cases/year in France vs. 0.41 for "Medical Interview"), but resulted in a decrease in annual costs of €2,203,000 (-42%). Base case and sub-group analysis showed that with the same effectiveness, the average cost per patient was: €13 with "Medical Interview" vs. €11.7 with TQS for the overall cohort; €28.9 with "Medical Interview" vs. €21 with "TQS" for tetanus-prone wounds; €15 with "Medical Interview" vs. €14.1 with "TQS" for patients aged ≥65 years; and €6.2 with "Medical Interview" vs. €7.8 with "TQS" for non-tetanus-prone wounds., Conclusions: Use of TQS is as effective and less costly than "Medical Interview" when applied in ED to wounded patients with tetanus-prone wounds or aged ≥65 years. However, it is more expensive in patients with non-tetanus-prone wounds.

Tetanus is a bacterial infection caused by Clostridium tetani and most commonly presents as trismus or other muscle spasms. Despite the development of the tetanus toxoid vaccine, tetanus infection has not been eradicated. Additionally, while there are hypothesized protective levels of tetanus antibody, tetanus infection may still occur in properly vaccinated individuals. We report the case of a 31-year-old male that presented to the emergency department (ED) with a 2-day history of neck and jaw pain. He reports puncturing his hand with a rusty nail 10 days prior. His reported vaccination history was that he received his last booster vaccination 13 years prior to presentation. In the ED, tetanus vaccine, tetanus immune globulin, and metronidazole were administered. His symptoms improved over the next 2 days and resolved at day 6. Despite his presentation of tetanus infection and rule out of other causes for his symptoms, his tetanus antibody level was reported at 8.4 U/mL, which is considered to be protective.A tetanus antibody level that is adequate for protective immunity should not preclude a patient from treatment of tetanus infection. This case demonstrates that a thorough history, physical exam, and rule out of other causes should guide treatment when there is concern for a tetanus infection.

To evaluate immunity to vaccine-preventable diseases according to nutritional status, a longitudinal study was conducted in Senegalese children ages 1-9 years old. A linear regression analysis predicted that weight for age was positively associated with immunoglobulin G (IgG) response to tetanus toxoid in children born during the rainy season or at the beginning of the dry season. A relationship between village, time of visits, and levels of antibodies to tetanus showed that environmental factors played a role in modulating humoral immunity to tetanus vaccine over time. Moreover, a whole-blood stimulation assay highlighted that the production of interferon-γ (IFN-γ) in response to tetanus toxoid was compromised in stunted children. However, the absence of cytokine modulation in response to Mycobacterium tuberculosis-purified protein derivatives and phytohemagglutinin suggests that the overall ability to produce IFN-γ was preserved in stunted children. Therefore, these results show that nutritional status can specifically alter the efficacy of long-lasting immunity to tetanus.

Background and Aims: Trans-placentally acquired antibodies can protect infants from infection in the first months of life. However, high concentrations of antibody at birth may impact the infant's own immune response to primary immunization. We examine the relationship between concentration of specific antibody to Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid and pneumococcal antigens at birth and following primary immunization., Methods: Healthy mother-infant pairs were recruited from a UK maternity unit. Peripheral blood samples were obtained at birth and 4 weeks after primary immunization. Specific antibody concentrations were determined using enzyme-linked immunosorbent assays. Pertussis antibody concentrations >50 IU/ml, Tetanus antibody levels >0.1 IU/ml and Hib antibody levels >0.15 mg/l were regarded as protective., Results: Following primary immunization, 35/36 (97%) infants had specific antibody concentrations associated with protection against Hib, 32/36 (89%) against pertussis and 36/36 (100%) against tetanus. Concentrations of all specific antibodies were significantly higher than at birth (p<0.0001), except anti-tetanus toxoid, p=0.41. However, there was an inverse correlation between infant antibody concentration at birth and fold-increase in antibody concentration post-immunization for tetanus: rs -0.86 (95%CI -0.93 to -0.74), p<0.0001; pneumococcus: rs -0.82 (95% CI -0.91 to -0.67), p<0.0001; pertussis: rs -0.77 (95% CI -0.89 to -0.58), p<0.0001 and Hib: rs -0.66 (95%CI -0.82 to -0.42), p<0.0001. The highest concentrations of specific IgG at birth were associated with lower concentrations post-immunization for tetanus (p=0.009) and pneumococcus (p=0.03). This association was not observed for Hib (p=0.88) or pertussis (p=0.14)., Conclusion: Higher antibody concentration at birth appeared to inhibit the response to infant immunization for tetanus and pneumococcus; the effect was less marked for Hib and pertussis. However, the majority of infants achieved high antibody levels post-immunization. This supports maternal immunization, as high levels of maternally derived antibody at birth may not inhibit infants' immunization responses in a clinically relevant manner., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Tetanus can be prevented by vaccination, which is especially important for overseas travelers. However, despite booster vaccination every 10 years being recommended, most Japanese adults do not receive it in the absence of physical injury or overseas travel. We aimed to investigate the level of protective immunity against tetanus among Japanese travelers, which may provide valuable information for formulating booster vaccination recommendations. 113 Japanese travelers given tetanus toxoid were recruited. The collected samples included paired samples prior to and 3-5 weeks after receiving the booster vaccination. Travelers who did not return and those lacking sample collection at the second visit were excluded. Finally, 96 paired blood samples were collected. History of immunization against tetanus, including DPT and DT vaccines, was determined from interviews or immunization records. The pre-vaccination geometric mean titer for the 96 participants was 1.07 IU/mL; 76% had a protective antitoxin level (>0.1 IU/mL), and 50% had a long-term protective antitoxin level (>1.0 IU/mL). Most participants <40 years old had protective immunity without receiving booster vaccination, whereas only 30.8% of those >50 years of age had protective immunity. Among the 23 participants without protective antitoxin levels (<0.1 IU/mL), booster vaccination was efficient in 100% of those <40 years but in only 28.6% of those >50 years of age. Although the tetanus antitoxin level decreases with age, booster vaccination helped to achieve an adequate protective antitoxin levels in Japanese travelers <40 years of age. Furthermore, the individuals who have never been vaccinated against tetanus especially in those >50 years old need to obtain protective immunity against tetanus according to a basic immunization schedule to prevent tetanus in travelers and residents of Japan., (Copyright © 2013 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: A 4-dose series of recently licensed Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was immunogenic with a clinically acceptable safety profile in infants, with antibodies persisting in most participants for 1 year following dose 4. This study assessed antibody persistence up to 5 years after vaccination., Methods: Participants had received HibMenCY-TT or Hib-TT at 2, 4 and 6 months of age. At age 12-15 months, HibMenCY-TT vaccinees received a fourth HibMenCY-TT dose (HibMenCY x 4 group), whereas those who received Hib-TT received a fourth dose of either Hib-TT (Hib) or HibMenCY-TT (HibMenCY x 1). Blood samples were collected 1 month and 1, 3 and 5 years after the last dose for measurement of antipolyribosylribitol phosphate (the Hib capsular polysaccharide) antibodies and serum bactericidal activity (human complement source) against meningococcal serogroups C and Y., Results: Five years after the fourth dose, the percentages of children with antipolyribosylribitol phosphate ≥0.15 μg/mL in HibMenCY x 4, HibMenCY x 1 and Hib groups were 98.8% (95% confidence interval: 93.5%-100%), 97.3% (85.8%-99.9%) and 92.3% (79.1%-98.4%), respectively. The percentages with human complement serum bactericidal activity ≥1:8 for meningococcal serogroup C were 82.9% (72.5%-90.6%), 73.5% (55.6%-87.1%) and 21.1% (9.6%-37.3%), respectively. The percentages with human complement serum bactericidal activity ≥1:8 for serogroup Y were 69.5% (58.4%-79.2%), 54.3% (36.6%-71.2%) and 18.4% (7.7%-34.3%), respectively., Conclusions: HibMenCY-TT given as a 4-dose series or as a single dose at 12-15 months of age induced immune responses for all 3 antigens that lasted for up to 5 years after vaccination in more than half of recipients.