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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.

Background: Diphtheria is a re-emerging infectious disease and public health concern worldwide and in Vietnam with increasing cases in recent years. This study aimed to assess the anti-diphtheria toxoid antibodies status in Khanh Hoa Province and identify factors contributing to the vaccination policy in the south-central coast of Vietnam., Methods: This was a cross-sectional study to evaluate the seroprevalence of anti-diphtheria toxoid antibodies among 1,195 participants, aged 5 - 40 years in Khanh Hoa Province, Vietnam. Immunoglobulin G antibody levels against diphtheria were detected using a commercial anti-diphtheria toxoid enzyme-linked immunosorbent assay (SERION ELISA classic Diphtheria Immunoglobulin G) and were categorized following the World Health Organization guidelines., Results: The mean anti-diphtheria toxoid antibody levels were 0.07 IU/ml (95% Confidence Interval: 0.07-0.08). Anti-diphtheria toxoid antibody levels were found to be associated with age and history of diphtheria vaccination. The 5-15 years age group had the highest levels (0.09 IU/ml), while the older age group had the lowest antibody level (p < 0.001). Individuals who received three doses (adjusted Odds ratio: 2.34, 95%CI: 1.35 - 4.07) or 4 + doses (adjusted Odds ratio: 2.45, 95%CI: 1.29 - 4.64) had a higher antibody level compared to those who received only one dose regardless of age., Conclusion: It is crucial to promote routine vaccination coverage to over 95% for children under one year of age with three primary doses of the diphtheria-containing vaccine, including additional doses at 18 months and 7 years of age. Booster doses should be promoted and administered to adolescents and adults every 10 years., (© 2024. The Author(s).)

Background: Ensuring vaccination coverage reaches established herd immunity thresholds (HITs) is the cornerstone of any vaccination programme. Diverse migrant populations in European countries have been associated with cases of vaccine-preventable diseases (VPDs) and outbreaks, yet it is not clear to what extent they are an under-immunized group., Methods: We did a systematic review and meta-analysis to synthesize peer-reviewed published primary research reporting data on the immune status of migrants in EU/EEA countries, the UK and Switzerland, calculating their pooled immunity coverage for measles, mumps, rubella and diphtheria using random-effects models. We searched on Web of Science, Embase, Global Health and MEDLINE (1 January 2000 to 10 June 2022), with no language restrictions. The protocol is registered with PROSPERO (CRD42018103666)., Findings: Of 1103 abstracts screened, 62 met eligibility criteria, of which 39 were included in the meta-analysis. The meta-analysis included 75 089 migrants, predominantly from outside Europe. Pooled immunity coverage among migrant populations was well below the recommended HIT for diphtheria (n = 7, 57.4% [95% confidence interval (CI): 43.1-71.7%] I2 = 99% vs HIT 83-86%), measles (n = 21, 83.7% [95% CI: 79.2-88.2] I2 = 99% vs HIT 93-95%) and mumps (n = 8, 67.1% [95% CI: 50.6-83.6] I2 = 99% vs HIT 88-93%) and midway for rubella (n = 29, 85.6% [95% CI: 83.1-88.1%] I2 = 99% vs HIT 83-94%), with high heterogeneity across studies., Interpretation: Migrants in Europe are an under-immunized group for a range of important VPDs, with this study reinforcing the importance of engaging children, adolescents and adults in 'catch-up' vaccination initiatives on arrival for vaccines, doses and boosters they may have missed in their home countries. Co-designing strategies to strengthen catch-up vaccination across the life course in under-immunized groups is an important next step if we are to meet European and global targets for VPD elimination and control and ensure vaccine equity., (© International Society of Travel Medicine 2024. Published by Oxford University Press.)

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies., Importance: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk., Competing Interests: The authors declare no conflict of interest.

Background: Diphtheria is rare in England because of an effective national immunisation schedule that includes 5 doses of a diphtheria-containing vaccine at 2, 3, 4 months, preschool and adolescent boosters. However, in recent years there has been a notable increase in cases due to Corynebacterium ulcerans among older adults and evidence of endemic transmission of C. diphtheriae (normally associated with travel to endemic countries). We aimed to update 2009 estimates of diphtheria immunity considering the evolving epidemiology., Methods: Residual sera collected from diagnostic laboratories and general practitioners in England in 2021 were randomly selected and tested for diphtheria antibody, to estimate proportions protected per age group. Diphtheria antibody levels were defined as susceptible (<0.01 IU/mL), basic protection (0.01-0.099 IU/mL) and full protection (≥0.1 IU/mL). Immunity estimates were standardised to the England population and compared to 2009., Results: Based on 3,745 residual sera tested, 89% (95%CI: 87%-90%) of the 2021 England population had at least basic diphtheria protection (vs. 90% [88%-92%] in 2009) and 50% (48%-52%) full protection (vs. 41% [38%-44%]). Higher antibody levels were observed in those aged 1 and under, 10-11, 12-15, 25-34 and 35-44 years compared to 2009. The largest proportion susceptible were observed in those aged 70+, 26% (21%-31%) vs 12% (7%-18%) in 2009., Conclusions: Basic diphtheria protection is comparable between 2021 and 2009. The increase in immunity in working age adults is likely due to the school leaver booster introduced in 1994. The current vaccination schedule is maintaining sufficient population immunity. However, we recommend clinicians remain vigilant to severe diphtheria outcomes in older adults, because of their observed susceptibility., Competing Interests: Declaration of Competing Interest The 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., (Crown Copyright © 2023. 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.)

Importance: New-onset retinal vascular occlusion (RVO) occurring acutely after messenger RNA (mRNA) COVID-19 vaccination has been described in recent literature. Because RVO can cause vision loss or blindness, an epidemiologic investigation evaluating this potential association is of great importance to public health., Objective: To investigate how often patients are diagnosed with new RVO acutely after the mRNA COVID-19 vaccine compared with influenza and tetanus, diphtheria, pertussis (Tdap) vaccines., Design, Setting, and Participants: A retrospective population-based cohort design using the TriNetX Analytics platform, a federated, aggregated electronic health record (EHR) research network containing the deidentified EHR data of more than 103 million patients, was used to examine aggregate EHR data. Data were collected and analyzed on October 20, 2022. Data on patients within the TriNetX Analytics platform were searched for the presence of vaccination Common Procedural Technology codes, and instances of newly diagnosed RVO within 21 days of vaccination were recorded and reported. Propensity score matching based on demographic characteristics (age, sex, race and ethnicity) and comorbidities (diabetes, hypertension, and hyperlipidemia) was performed between vaccination groups for evaluation of relative risks (RRs)., Main Outcomes and Measures: The appearance of a new-encounter diagnosis of RVO within 21 days of the mRNA COVID-19 vaccination was the primary outcome. Historical comparison cohorts of patients receiving influenza and Tdap vaccinations allowed for evaluation of the RRs for RVO., Results: Of 3 108 829 patients (mean [SD] age at vaccination, 50.7 [20.4] years; 56.4% women) who received the mRNA COVID-19 vaccine, 104 (0.003%; 95% CI, 0.003%-0.004%) patients had a new diagnosis of RVO within 21 days of vaccination. After propensity score matching, the RR for new RVO diagnosis after the first dose of COVID-19 vaccination was not significantly different from that after influenza (RR, 0.74; 95% CI, 0.54-1.01) or Tdap (RR, 0.78; 95% CI, 0.44-1.38) vaccinations, but was greater when compared with the second dose of the COVID-19 vaccination (RR, 2.25; 95% CI, 1.33-3.81)., Conclusions and Relevance: The findings of this study suggest that RVO diagnosed acutely after mRNA COVID-19 vaccination occurs extremely rarely at rates similar to those of 2 different historically used vaccinations, the influenza and Tdap vaccines. No evidence suggesting an association between the mRNA COVID-19 vaccination and newly diagnosed RVO was found.

Diphtheria is a potentially devastating disease whose epidemiology remains poorly described in many settings, including Madagascar. Diphtheria vaccination is delivered in combination with pertussis and tetanus antigens and coverage of this vaccine is often used as a core measure of health system functioning. However, coverage is challenging to estimate due to the difficulty in translating numbers of doses delivered into numbers of children effectively immunised. Serology provides an alternative lens onto immunisation, but is complicated by challenges in discriminating between natural and vaccine-derived seropositivity. Here, we leverage known features of the serological profile of diphtheria to bound expectations for vaccine coverage for diphtheria, and further refine these using serology for pertussis. We measured diphtheria antibody titres in 185 children aged 6-11 months and 362 children aged 8-15 years and analysed them with pertussis antibody titres previously measured for each individual. Levels of diphtheria seronegativity varied among age groups (18.9% of children aged 6-11 months old and 11.3% of children aged 8-15 years old were seronegative) and also among the districts. We also find surprisingly elevated levels of individuals seropositive to diphtheria but not pertussis in the 6-11 month old age group suggesting that vaccination coverage or efficacy of the pertussis component of the DTP vaccine remains low or that natural infection of diphtheria may be playing a significant role in seropositivity in Madagascar.

Background: Although the combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is recommended at adolescence in developed countries, the tetanus and diphtheria toxoid vaccine (Td), which is less costly, is recommended instead in some parts of the world. A new Td, BR-TD-1001, was developed by a Korean manufacturer for distribution to endemic regions and for use in the initial step of novel Tdap development., Methods: This phase 3, randomized, double-blind, multi-center trial, conducted in Korea, aimed to evaluate the immunogenicity and safety of BR-TD-1001. Healthy children aged 10 to 12 years were randomized 1:1 to receive either BR-TD-1001 or the control Td (Td-pur, GlaxoSmithKline). Antibodies were measured using enzyme-linked immunosorbent assay., Results: A total of 218 subjects (BR-TD-1001, n = 108; control, n = 110) were enrolled and included in the safety analysis. Vaccine-mediated antibody responses were similar in both groups. We confirmed the non-inferiority of BR-TD-1001 against the control, Td; 100% of both groups achieved seroprotection against diphtheria and tetanus. Furthermore, there was no significant difference between groups in the proportion of participants who demonstrated boost responses against diphtheria and tetanus toxoids. The incidence of solicited local and systemic adverse events (AEs), unsolicited AEs, and serious AEs did not differ significantly between groups., Conclusion: The BR-TD-1001 satisfied the immunological non-inferiority criterion against diphtheria and tetanus, with a clinically acceptable safety profile., Trial Registration: ClinicalTrials.gov Identifier: NCT04618939., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background: Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population., Patients and Methods: Patients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks., Results: Fifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG., Conclusions: Patients with CLL demonstrate humoral immunodeficiency despite IgG > 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs., Clinical Trials Registration: NCT03730129., Competing Interests: The authors have read the journal’s policy and have the following competing interests: CSL Behring provided support for this study in the form of an investigator-initiated grant awarded to SSM. SSM is on the speaker’s bureau for CSL Behring, Genentech, Regeneron, and AstraZeneca. AR is on the speaker’s bureau for Regeneron. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Early studies on vaccination of children with oncological diseases were only dedicated to the assessment of safety and immunogenicity of the drug. Mechanisms of the post-vaccination immune response were not investigated. This study involved 41 patients aged 7-15 years who were treated for solid tumors two or more years ago. Of these, 26 were vaccinated against diphtheria and tetanus with ADS-m toxoid. Fifteen children (i.e., controls) were not vaccinated. The vaccination tolerability and clinical characteristics of the underlying disease remission ware assessed. Lymphocyte subpopulations were investigated over time by flow cytometry at 1, 6, and 12 months. IgG anti-diphtheria and anti-tetanus toxoids levels were assessed by ELISA. Within the first day of the post-vaccination period, two (7.7%) children demonstrated moderate local reactions and increased body temperature (up to 38.0°C). Relapse and metastasis were not mentioned within a year after immunization. An increase in concentration of IgG antibodies, maintained for 12 months, were noted [2.1 (1.3-3.4) IU/ml against diphtheria (p <0.001), 6.4 (2.3-9.7) IU/ml against tetanus (p <0.001)]. In contrast to healthy children, those with a history of cancer demonstrated a decrease in the relative number of mature T lymphocytes, as well as in absolute number of cytotoxic T cells and B lymphocytes. In a month after the revaccination, a significant increase in absolute (p = 0.04) and relative (p = 0.007) numbers of T lymphocytes and T helpers was revealed. In a year, these values decreased to baseline levels. As for helpers, they decreased below baseline and control values (p = 0.004). In a year after the vaccination, there was a significant (p = 0.05) increase in lymphocyte level with a decrease in the number of NK cells and B cells as compared with controls. Revaccination against diphtheria and tetanus promoted proliferation of a total lymphocytic cell pool along with restoration of the T lymphocyte subpopulation in children with a history of solid tumors. The ADS-m toxoid has a certain nonspecific immunomodulatory effect. These findings are important, also in the midst of the coronavirus pandemic., 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 Kostinov, Akhmatova, Karpocheva, Vlasenko, Polishchuk and Kostinov.)

Background: Diphtheria is re-emerging as a public health problem in several Indian states. Most diphtheria cases are among children older than 5 years. In this study, we aimed to estimate age-specific immunity against diphtheria in children aged 5-17 years in India., Methods: We used residual serum samples from a cross-sectional, population-based serosurvey for dengue infection done between June 19, 2017, and April 12, 2018, to estimate the age-group-specific seroprevalence of antibodies to diphtheria in children aged 5-17 years in India. 8309 serum samples collected from 240 clusters (122 urban and 118 rural) in 60 selected districts of 15 Indian states spread across all five geographical regions (north, northeast, east, west, and south) of India were tested for the presence of IgG antibodies against diphtheria toxoid using an ELISA. We considered children with antibody concentrations of 0·1 IU/mL or greater as immune, those with levels less than 0·01 IU/mL as non-immune (and hence susceptible to diphtheria), and those with levels in the range of 0·01 to less than 0·1 IU/mL as partially immune. We calculated the weighted proportion of children who were immune, partially immune, and non-immune, with 95% CIs, for each geographical region by age group, sex, and area of residence (urban vs rural)., Findings: 29·7% (95% CI 26·3-33·4) of 8309 children aged 5-17 years were immune to diphtheria, 10·5% (8·6-12·8) were non-immune, and 59·8% (56·3-63·1) were partially immune. The proportion of children aged 5-17 years who were non-immune to diphtheria ranged from 6·0% (4·2-8·3) in the south to 16·8% (11·2-24·4) in the northeast. Overall, 9·9% (7·7-12·5) of children residing in rural areas and 13·1% (10·2-16·6) residing in urban areas were non-immune to diphtheria. A higher proportion of girls than boys were non-immune to diphtheria in the northern (17·7% [12·6-24·2] vs 7·1% [4·1-11·9]; p=0·0007) and northeastern regions (20·0% [12·9-29·8] vs 12·9% [8·6-19·0]; p=0·0035)., Interpretation: The findings of our serosurvey indicate that a substantial proportion of children aged 5-17 years were non-immune or partially immune to diphtheria. Transmission of diphtheria is likely to continue in India until the immunity gap is bridged through adequate coverage of primary and booster doses of diphtheria vaccine., Funding: Indian Council of Medical Research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Reported incidence of pertussis in the European Union (EU) and the European Economic Area (EEA) varies and may not reflect the real situation, while vaccine-induced protection against diphtheria and tetanus seems sufficient. We aimed to determine the seroprevalence of DTP antibodies in EU/EEA countries within the age groups of 40-49 and 50-59 years. Eighteen countries collected around 500 samples between 2015 and 2018 (N = 10,302) which were analysed for IgG-DTP specific antibodies. The proportion of sera with pertussis toxin antibody levels ≥100 IU/mL, indicative of recent exposure to pertussis was comparable for 13/18 countries, ranging between 2.7-5.8%. For diphtheria the proportion of sera lacking the protective level (<0.1 IU/mL) varied between 22.8-82.0%. For tetanus the protection was sufficient. Here, we report that the seroprevalence of pertussis in these age groups indicates circulation of B. pertussis across EU/EEA while the lack of vaccine-induced seroprotection against diphtheria is of concern and deserves further attention.

The dawn of the 20th century saw the formative years of developments in immunology. In particular, immunochemistry, specifically pertaining to antibodies, was extensively studied. These studies laid the foundations for employing antibodies in a variety of ways. Not surprisingly, antibodies have been used for applications ranging from biomedical research to disease diagnostics and therapeutics to evaluation of immune responses during natural infection and those elicited by vaccines. Despite recent advancements in cellular immunology and the excitement of T cell therapy, use of antibodies represents a large proportion of immunotherapeutic approaches as well as clinical interventions. Polyclonal antibodies in the form of plasma or sera continue to be used to treat a number of diseases, including autoimmune disorders, cancers, and infectious diseases. Historically, antisera to toxins have been the longest serving biotherapeutics. In addition, intravenous immunoglobulins (IVIg) have been extensively used to treat not only immunodeficiency conditions but also autoimmune disorders. Beyond the simplistic suppositions of their action, the IVIg have also unraveled the immune regulatory and homeostatic ramifications of their use. The advent of monoclonal antibodies (MAbs), on the other hand, has provided a clear pathway for their development as drug molecules. MAbs have found a clear place in the treatment of cancers and extending lives and have been used in a variety of other conditions. In this review, we capture the important developments in the therapeutic applications of antibodies to alleviate disease, with a focus on some of the recent developments.

Objectives: The aim of this study was to evaluate the development and status quo of the quality of high throughput in vitro diagnostic testing for tetanus and diphtheria antitoxin antibody (ATX) concentrations based on external quality assessment (EQA) data., Methods: We analyzed manufacturer-specific data of 22 EQA surveys-each for the detection of tetanus and diphtheria ATX-to check the diagnostic strength of the corresponding in vitro diagnostic systems., Results: While the results were mostly well aligned, individual surveys showed widely dispersed ATX concentrations. The medians of manufacturer collectives deviated from the overall median by up to 8.9-fold in the case of diphtheria ATX and by up to 3.5-fold in the case of tetanus ATX. Such a distribution in the results is particularly critical in the cut-off range for immunity and may lead to an incorrect assessment of vaccination status., Conclusion: These results were surprising as there are International Standards for both ATX; however, the results may be linked to the high ATX concentration of the reference material, which deviates considerably from clinically significant concentrations. To increase the accuracy and diagnostic strength of both assays, we recommend a recalibration of the test systems and verification of their traceability to the International Standards., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Bacillus Calmette-Guérin (BCG), the only vaccine against tuberculosis (TB) currently in use, has shown beneficial effects against unrelated infections and to enhance immune responses to vaccines. However, there is little evidence regarding the influence of BCG vaccination on pertussis., Methods: Here, we studied the ability of BCG to improve the immune responses to diphtheria, tetanus, and acellular (DTaP) or whole-cell pertussis (DTwP) vaccination in a mouse model. We included MTBVAC, an experimental live-attenuated vaccine derived from Mycobacterium tuberculosis, in our studies to explore if it presents similar heterologous immunity as BCG. Furthermore, we explored the potential effect of routine BCG vaccination on pertussis incidence worldwide., Findings: We found that both BCG and MTBVAC when administered before DTaP, triggered Th1 immune responses against diphtheria, tetanus, and pertussis in mice. Immunization with DTaP alone failed to trigger a Th1 response, as measured by the production of IFN-γ. Humoral responses against DTaP antigens were also enhanced by previous immunization with BCG or MTBVAC. Furthermore, exploration of human epidemiological data showed that pertussis incidence was 10-fold lower in countries that use DTaP and BCG compared to countries that use only DTaP., Interpretation: BCG vaccination may have a beneficial impact on the protection against pertussis conferred by DTaP. Further randomized controlled trials are needed to properly define the impact of BCG on pertussis incidence in a controlled setting. This could be a major finding that would support changes in immunization policies., Funding: This work was supported by the Ministry of "Economía y Competitividad"; European Commission H2020 program, "Gobierno de Aragón"; CIBERES; "Fundação Butantan"; Instituto de Salud Carlos III and "Fondo FEDER"., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Type I IFNs are a range of host-derived molecules with adjuvant potential; they have been used for many years in the treatment of cancer and viral hepatitis. Therefore, the safety of IFNs for human use has been established. In this study, we evaluated the mucosal adjuvanticity of IFN-β administered intranasally to mice with diphtheria toxoid, and suggested a method to improve its adjuvanticity. When IFN-β alone was used as a mucosal adjuvant, no clear results were obtained. However, simultaneous administration of IFN-β and chitosan resulted in an enhancement of the specific serum immunoglobulin G (IgG) and IgA antibody responses, the mucosal IgA antibody response, and antitoxin titers. Furthermore, the intranasal administration of IFN-α alone resulted in a greater increase in antibody titer than IFN-β, and a synergistic effect with chitosan was also observed. These findings suggest that intranasal administration of chitosan and Type I IFNs may display an effective synergistic mucosal adjuvant activity., (© 2020 The Societies and John Wiley & Sons Australia, Ltd.)

Background: Globally, the use of single DTaP-IPV/Hib vaccines that combine DTaP-IPV and Hib is widespread, but in Japan vaccination is usually concomitant at separate sites. The immunogenicity and safety of a primary vaccination series and booster of a combined pentavalent DTaP-IPV/Hib vaccine were evaluated and compared to separate administration of DTaP-IPV and Hib in Japanese infants., Methods: Healthy Japanese infants were administered DTaP-IPV/Hib (Group A: N = 207) or DTaP-IPV + Hib (Group B: N = 207) by the subcutaneous (SC) or DTaP-IPV/Hib by the intramuscular (IM) route (Group C: N = 10). All subjects received a 3-dose primary vaccination series and a booster. Non-inferiority (Group A versus Group B) was tested post-primary series and subsequent post hoc analyses were performed for anti-Hib. Safety was assessed by parental reports., Results: Non-inferiority for SC administration of Group A versus Group B for the primary series was demonstrated for antibody responses to all antigens except Hib using the threshold of 1.0 μg/mL. Post hoc analyses for anti-Hib demonstrated non-inferiority for the primary series response using 0.15 μg/mL, and for pre-booster antibody persistence and the booster response using 0.15 μg/mL and 1.0 μg/mL. The immune response was similar for each antigen following SC or IM administration. There were no safety concerns in any group, and a lower incidence of injection sites for the IM route was observed as expected., Conclusions: These data show the good immunogenicity and safety profile of the DTaP-IPV/Hib vaccine as a 3-dose infant primary series followed by a booster in the second year of life in Japan., Competing Interests: Declaration of Competing Interest TN is a consultant to Daiichi Sankyo and Kitasato Daiichi Sankyo Vaccines and received a research grant from Daiichi Sankyo and Kitasato Daiichi Sankyo Vaccines; EV is an employee of Sanofi Pasteur, DT, SN, TS, YI, and HM are employees of Sanofi; HT is an employee of Daiichi Sankyo., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The objective was to investigate the immune status against tetanus and diphtheria of healthcare workers in Catalonia. A cross-sectional multicentre study was conducted in seven health centres. Blood samples were obtained, and demographic and clinical variables collected. 509 health workers were included. The prevalence of protective antibodies against tetanus was 94.7% (95% CI: 92.3-96.4) overall and 85.1% (95% CI: 74.5-92.0) in workers aged ≥55 years. The prevalence of protective antibodies against diphtheria was 68.6% (95% CI: 64.3-72.5%) overall and 29.7% (95% CI: 19.9-41.6) in workers aged ≥55 years. Protection against tetanus in healthcare workers is high, but should be improved in workers aged ≥55 years. Protection against diphtheria has improved in healthcare workers over the past decade (68.6% vs 46.5%) but should be improved in all ages, especially in workers aged ≥55 years., Competing Interests: Declaration of Competing Interest The 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 © 2020 Elsevier Ltd. All rights reserved.)

Objectives: We report the results of the 2007 national serological survey of immunity to diphtheria in Australia to assess the impact of recent schedule changes on diphtheria immunity, and the adequacy of current policy in the context of increased international travel of people and pathogens., Methods: Residual sera (n =1656) collected opportunistically from Australian laboratories in 2007 were tested for diphtheria antibody levels using an enzyme immunoassay, with the protective threshold defined as ≥0.1 IU/mL. About 40% of adults aged ≥30 years are susceptible to diphtheria; following the removal of the 18-month booster and its replacement with a dose in adolescence offered through school-based dTpa vaccination program, 59% of children aged 3 years were susceptible to diphtheria, whilst adolescents demonstrated improved immunity., Results: There is no apparent boosting of diphtheria immunity from meningococcal group C conjugate (MCC) or seven-valent pneumococcal conjugate (7vPCV) vaccines in relevant age groups., Conclusion: Australians who travel to diphtheria-endemic areas should be up-to-date with their vaccinations. Close monitoring of population immunity levels against diphtheria remains important to ensure that immunity does not decline to a level where wide-spread transmission would be possible., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Passive transferred antibodies to the fetus play an essential role on protecting neonates and young infants until infant vaccination is more efficacious. However, very little is known about the discrepancy of DTP vaccine associated antibodies level in neonates from different economic areas in China., Methods: In 2018, 200 neonates hospitalized in Shunyi Women and Children's Hospital in Beijing, and 238 neonates hospitalized in Qianjiang Central Hospital located in the southwestern mountainous areas were included in this study. Antibodies specific for the antigens covered by DTP vaccine were determined using ELISA Kits (Euroimmun, Lübeck, Germany). The cut off value of ≥0.1 IU/ml (anti-diphtheria, anti-Dtx), > 0.1 IU/ml (anti-tetanus, anti-Ttx) and > 40 IU/ml (anti-pertussis toxin, anti-Ptx) were used to assess the percentage of protected neonates, respectively., Results: The antibody levels in the neonates from Qianjiang (0.04 IU/ml for anti-Dtx IgG and 0.07 IU/ml for anti-Ttx IgG) were significantly lower than those from Shunyi (0.12 IU/ml for anti-Dtx IgG and 0.18 IU/ml for anti-Ttx IgG). The prevalence of protective anti-Dtx and anti-Ttx IgG were lower in the neonates from Qianjiang (7.1% for anti-Dtx IgG and 7.6% for anti-Ttx IgG) than in those from Shunyi (30.5% for anti-Dtx and 38.5% for anti-Ttx). The neonates from Qianjiang also had lower detectable rate of anti-Dtx (57.5%) and anti-Ttx IgG (55.8%) than neonates from Shunyi (97.5% for anti-Dtx and 71.0% for anti-Ttx). However, the detectable rate of anti-Ptx IgG in neonates from Qianjiang (39.9%) was higher significantly than in those from Shunyi (30.5%). Two neonates from Qianjiang have anti-PT IgG ≥100.0 IU/ml, which suggested that their mothers have a recent pertussis course., Conclusions: The regional discrepancy of the protective antibody rates might be caused by different vaccine coverage and pertussis exposure, which suggested the importance of Tdap booster immunization for pregnant women or women at childbearing age, those living undeveloped areas in particular.

Background: Owing to a declining birth rate and longer lifespan, the number of elderly people (≥ 60 years) in Thailand has grown rapidly. However, the elderly are at significant risk of infectious diseases because they have never been immunized, because they have not been completely immunized, or because their immunity has waned. Immunity against infectious diseases in the elderly is an important means of controlling diseases in the community. Our objective was to evaluate the seroprotective rate against diphtheria, tetanus, and pertussis in the elderly Thai population., Methods: In total, 430 healthy individuals from the northeastern region of Thailand were enrolled in this study and stratified into five age groups: 60-65, 66-70, 71-75, 76-80, and > 80 years. Serum samples were collected and quantitatively analyzed for diphtheria, tetanus, and pertussis IgG antibody by using commercial ELISA kits. For anti-diphtheria toxoid and anti-tetanus toxoid ELISA, values < 0.01 IU/ml were interpreted as seronegative, and for anti-Bordetella pertussis toxin ELISA, values < 5 IU/ml were interpreted as seronegative; these definitions were in accord with previous studies., Results: For diphtheria toxoid Ab, the majority of the population had antibody levels > 0.01 IU/ml. For tetanus anti-toxoid Ab, the majority of the population had antibody levels of > 0.01 IU/ml, of which approximately 34% had durable antibody protection levels (DAPL) of ≥ 1 IU/ml. Meanwhile, nearly 45% of the population had an Ab level against pertussis lower than the protectivity level., Conclusions: In total, 97.2%, 83.5%, and 55.8% of the population had a higher antibody level than the minimal protective level for diphtheria, tetanus, and pertussis, respectively. In order to prevent an outbreak of these diseases in the future, the elderly should be administered with Tdap revaccination to provide diphtheria herd immunity in the population; this will increase cocoon phenomenon for pertussis and protect the population from tetanus-prone injury.

Respiratory diphtheria is an acute respiratory tract infection. The high mortality rates (5-10%) are related to airway obstruction and local and systemic effects of the diphtheria toxin. Vaccination against diphtheria has been available through the Dutch national vaccination programme since the 1950s. The disease has now become rare as a result of herd immunity by these vaccinations. As a consequence, the disease has largely been forgotten, which can result in it not being recognised and treated in time. In addition, diphtheria antitoxin is not always available. In this article, we are drawing attention to the need for immunisation. We also look back at how diphtheria prevention started in the Netherlands.

Background: This study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) and the reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (Tdap) when co-administered in adults aged ≥50 years., Methods: In this open label, multi-center study (NCT02052596), participants were randomized 1:1 to the Co-Administration group (RZV dose 1 and Tdap at Day 0 [D0], RZV dose 2 at Month 2 [M2]) or Control group (Tdap at D0, RZV dose 1 at M2, RZV dose 2 at M4). Co-primary objectives were evaluation of the vaccine response rate (VRR) to RZV in the Co-Administration group, and demonstration of non-inferiority of the humoral responses to RZV and Tdap in the Co-Administration compared to Control group. Reactogenicity and safety of RZV and Tdap were also assessed., Results: VRR to RZV was 97.8% in the Co-Administration group. The non-inferiority criterion was met for the humoral response to RZV and for 4 Tdap antigens, but was not met for the Tdap antigen pertactin. Occurrences of solicited, unsolicited and serious adverse events, and potential immune-mediated diseases were similar between groups., Conclusions: Co-administration of RZV and Tdap did not interfere with the humoral immune response to RZV or 4 of the 5 Tdap antigens. No safety concerns were identified., (Copyright © 2019 GSK. Published by Elsevier Ltd.. All rights reserved.)

The possible risk of hyperimmunization after tetanus vaccination is currently discussed after the National Vaccine Prevention Plan 2017-2019 confirmed the recommendation of a booster dose every ten years. Due to the ubiquitous nature of tetanus spores and the inability to obtain herd-immunity through vaccination, efforts to reduce the incidence of tetanus aim at eliminating the disease. The only way to prevent infection is vaccination followed by recommended periodic booster doses. Between 2012 and 2016, Italy notified 45% (252/564) of all cases reported by the 26 EU Member States, most of them in the over 65 age group, generally women in the rural areas. The recommendation of the antipertussis vaccine, combined with anti-tetanus, in pregnancy and the indications for antitetanic prophylaxis by vaccination or specific immunoglobulins in emergency setting, gives rise to doubts about the risk of hyperimmunization. Studies generally agree on the safety of diphtheria-tetanus-pertussis combined vaccines during the third trimester of pregnancy, and the time elapsed since the previous tetanus vaccination seems not to be related to significant differences in the incidence of adverse events or obstetrical complications. In the emergency wards, given the relatively high incidence of tetanus in Italy, the risk/benefit ratio often leads to prefer vaccination to no-intervention. The administration of tetanus immunoglobulins in subjects not vaccinated in the last 10 years seems justified by the epidemiology of tetanus in Italy.

Introduction: Bacillus Calmette-Guérin vaccine (BCG), one of the most widely used vaccines, does not only provide protection against tuberculosis and other mycobacterial infections, but also has non-specific (heterologous) immunomodulatory effects. In participants in a randomised trial, we investigated the effect of neonatal BCG immunisation on antibody responses to routine infant vaccines given in the first year of life., Methods: Antibodies against antigens in the diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), and the 13-valent pneumococcal conjugate vaccines were measured in 91 (45 BCG-vaccinated, 46 BCG-naïve) infants one month after, and in 310 (169 BCG-vaccinated, 141 BCG-naïve) infants seven months after immunisation at 6 weeks, 4 and 6 months of age. In addition, antibodies against meningococcus C, Hib, measles, mumps, and rubella were measured in 147 (78 BCG-vaccinated, 69 BCG-naïve) infants one month after immunisation at 12 months of age. The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared in BCG-vaccinated and BCG-naïve infants., Results: At 7 months of age, seroprotection rates were high in both BCG-vaccinated and BCG-naïve infants. At 13 months of age, seroprotection rates were lower than at 7 months of age, particularly for pertussis and a number of pneumococcal antigens, with generally higher rates for the latter in BCG-vaccinated infants. Although not statistically significant, antibody responses in BCG-vaccinated infants were consistently higher against diphtheria, tetanus, and pneumococcal antigens at both 7 and 13 months of age, and against measles and mumps at 13 months of age, but were lower against Hib one month after immunisation at both 7 and 13 months of age., Conclusion: The immunomodulatory effect of BCG on antibody responses to heterologous vaccines adds to the evidence that BCG immunisation at birth has broad heterologous effects on the infant immune system., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Data on the serologic status of childhood vaccines, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are limited in inflammatory bowel disease (IBD). Therefore, we evaluated vaccine coverage and seroprotection, along with CMV and EBV seropositivity, in pediatric IBD., Methods: In a cross-sectional study, demographic data, IBD history, vaccine records, and serum for antibodies against measles, mumps, rubella, diphtheria, tetanus, varicella, hepatitis B (HBV), CMV, and EBV were collected from children with IBD. We evaluated potential factors associated with serologic status., Results: Of 156 subjects, vaccine coverage was up to date for age in 93.5% for measles, mumps, rubella, 95.6% for diphtheria, tetanus, pertussis, polio, hemophilus influenza B, 75.8% for HBV, and 93.5% for varicella, including past infection and vaccination. Seroprotection was present in 65.8% for measles, 60.5% for mumps, 79.1% for rubella, 79.5% for diphtheria, 80.8% for tetanus, 70.5% for varicella, and 62.8% for HBV of subjects. Older age at diagnosis was associated with seroprotection among subjects with complete HBV (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.03-1.39) and rubella series (OR, 1.18; 95% CI, 1.02-1.37). Older age at serum collection was associated with seroprotection among subjects with prior varicella vaccination or infection (OR, 1.69; 95% CI, 1.33-2.15). Only 25.2% and 37.8% demonstrated seropositivity to CMV and EBV, respectively. Among subjects on immunosuppressive medications, 75.3% and 62.4% were seronegative for CMV and EBV, respectively., Conclusions: Children with IBD have low serologic protection to childhood vaccines in spite of high vaccine coverage and universal vaccinations. Children with IBD, including a large proportion on immunosuppressive medications, have low seropositivity to CMV and EBV., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Despite high population immunity, pertussis remains one of the leading causes of vaccine-preventable deaths worldwide. The aim of this study was to determine the seroprevalence of IgG antibodies to pertussis toxin (PT) and diphtheria among the adult male population leaving or entering China., Methodology: Blood samples were obtained from 240 Chinese and 207 African healthy adults that were leaving and entering China, respectively. Serum IgG antibodies against PT (anti-PT IgG) and diphtheria were determined., Results: The mean concentration of anti-PT IgG antibodies was 13.82 IU/mL and 18.11 IU/mL for the leaving and entering populations, respectively. None of the studied Chinese leaving China were seropositive for pertussis. Of the 240 subjects leaving China, 209 (87.1%) had anti-diphtheria antibody concentrations of ≥ 0.1 IU/mL and 31 (12.9%) had antibody concentrations between 0.01 and 0.099 IU/mL. Eleven (5.31%) of the studied Africans entering China had anti-PT IgG antibodies higher than 30 IU/mL and thus were considered seropositive for pertussis. Of the 207 Africans entering China, antibody concentrations of ≥ 0.1 IU/mL were found in 164 subjects (79.2%) while 43 (20.8%) had antibody concentrations between 0.01 and 0.099 IU/mL., Conclusions: Almost all Chinese adult men leaving China and most African men entering China have very low serum antibody levels of pertussis. Furthermore, the antibody level of diphtheria among these two populations was low among adults. A larger population study is needed to determine whether booster vaccinations against pertussis and diphtheria should be considered for adults in China and also for Africans entering China., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Hui Han, Zhiqiang Fang, Xiangguang Ye, Hailei Wu, Feng Zuo, Quan Shi, Jinping Mu, Baoliang Xu.)

Serological assays detecting antibodies in serum or plasma samples are useful and versatile instruments to investigate an individual's infection and vaccination history, e.g. for clinical diagnosis, personal risk evaluation, and seroepidemiological studies. Multiplex Serology is a suspension bead array-based high-throughput methodology for simultaneous measurement of antibodies against multiple pathogens in a single reaction vessel, thus economizing sample volume, measurement time, and costs. We developed and validated bead-based pathogen-specific Monoplex Serology assays, i.e. assays including only antigens for the respective pathogen, to detect antibodies against Corynebacterium diphtheriae and Clostridium tetani toxins, rubella virus and parvovirus B19. The developed assays expand the portfolio of existing pathogen-specific bead-based serology assays and can be efficiently incorporated into larger Multiplex Serology panels. The newly developed Monoplex Serology assays consist of only one antigen per infectious agent, expressed as Glutathione S-transferase-fusion proteins in E. coli. Specificity, sensitivity and Cohen's kappa statistics in comparison with routine clinical diagnostic assays were calculated for serum dilutions 1:100 and 1:1000. All pathogen-specific assays were successfully validated at both serum dilutions with the exception of rubella Monoplex Serology which showed impaired sensitivity (57.6%) at dilution 1:1000. Specificities of successfully validated Monoplex Serology assays ranged from 85.6% to 100.0% (median: 91.7%), and sensitivities from 81.3% to 95.8% (median: 90.9%); agreement with the reference assays ranged from substantial to almost perfect (kappa: 0.66-0.86, median: 0.78). Statistical performance and slim assay design enable efficient incorporation of the developed assays into Multiplex Serology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We describe here a magnetic bead-based multiplex (pentaplex) immunoassay (MIA) platform developed as an alternative to enzyme-linked immunosorbent assays (ELISA) used in immunogenicity testing of DTaP/TdaP vaccine in animals. MIA simultaneously measures the concentration of serum (IgG) antibodies against B. Pertussis antigens; pertussis toxin, filamentous hemagglutinin (FHA), pertactin (PRN) and tetanus (T) and diphtheria (D) toxoid in the Tdap vaccine immunized animals. Assay validation experiments were done using a panel of serum samples. The results are expressed in IU/ml using WHO reference mice serum. The standard curve was linear with 4PL logistic fit over an eight 2-fold dilution range with LOQ of 0.003, 0.022, 0.005 IU/ml for PT, FHA and PRN and 0.016 U/ml for T and D antigens indicating sensitivity. No interference was observed in monoplex versus multiplex measurements. Specificity was demonstrated by ≥90% homologous and ≤15% heterologous inhibition for all the antigens. The assay was reproducible, with a mean coefficient of variation (CV) of ≤10% for intra-assay duplicates and ≤25% for interassays using different lots of beads and analyst. Accuracy was demonstrated wherein the ratio of observed vs. assigned unitages were within 80-120%. The study suggests that the Pentaplex (MIA) platform meets all the criteria for the serological assay combination vaccines with additional advantages of high throughput, reduced sample volumes, faster analysis with reduced manpower in contrast to conventional monoplex ELISA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Developmental exposure to perfluorinated alkylate substances (PFASs) is associated with deficient IgG antibody responses to childhood vaccines. As this immunotoxicity outcome may represent a critical effect, calculation of benchmark dose (BMD) results would be useful for defining protective limits of exposure. However, exposures to the major PFASs that are associated with this adverse effect are interrelated, and mutually adjusted BMD results would be desirable., Methods: We carried out BMD calculations on prospective data from two prospective birth cohort studies from the Faroe Islands with a total of 1,146 children. Exposure data included serum concentrations of five major PFASs at birth and at age 5 years and, as outcome parameters, the serum concentrations of specific IgG antibodies against tetanus and diphtheria at ages 5 and 7. We calculated the BMDs and their lower confidence bounds (BMDLs) and included mutual adjustment for five major PFASs. BMD and BMDL were expressed in terms of the serum concentration of the PFASs., Results: The BMDLs for the immunotoxicants were of similar magnitude before and after adjustment. As compared to linear dose-response models, the PFASs showed lower results for a piecewise linear model, which also provided a slightly better fit. Weaker associations with the antibody outcomes were observed after adjustments due to the correlation between the PFASs. However, while the adjustments resulted in elevated BMD results and p values, the BMDL values were not materially changed., Conclusions: Adjustment for co-exposure to a related immunotoxicant increased both the BMD values and their standard errors, though affected the BMDL values only to a negligible extent. Thus, when correlated toxicants appear to affect the same outcome and none of them is known a priori to be solely responsible, all exposures may be considered responsible in BMD calculations. Our BMDL results, both before and after adjustment are generally below current exposure levels and therefore suggest that all five perfluorinated substances should attract regulatory attention, at least until additional evidence shows otherwise., Competing Interests: Apart from PG having served as health expert for the State of Minnesota in a lawsuit, which does not affect the adherence to all PLOS ONE policies, the authors have no competing interests to declare, financial or otherwise.

Background: Over the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease., Methods: This phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy., Results: 1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised., Conclusion: A second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated., (Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Provenance: internally peer-reviewed

Immunogenicity of 13-valent pneumococcal polysaccharide (PnPS) conjugate vaccine (PCV13) was evaluated in 38 rheumatoid arthritis patients under immunosuppressive treatment and 20 healthy controls (HC). Antibodies to all PnPS and diphtheria-toxin analogue conjugate protein were measured pre- (T0), 1 (T1), 6 (T2), 12 (T3) months post-immunization. Patients and HC had similar response to individual PnPS. Mean antibody levels to all PnPS but one doubled at T1 compared with T0, with T3 persistence for only 8-7/13 PnPS. Baseline antibody levels was inversely associated with the rate of responders at T1 (T1/T0≥2) to 11/13 PnPS. Few subjects reached protective IgG levels against some serotypes frequently isolated in Italian patients with invasive pneumococcal disease. Antibody response was not influenced by therapy, except the one to PS7F, which was reduced by tumor necrosis factor-α-inhibitors. Vaccination increased also anti-diphtheria IgG. Despite this study substantially confirmed the PCV13 immunogenicity in immunocompromised patients, it also revealed some limitations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pneumococcus is a common cause of invasive and non-invasive infections in children. In areas with high vaccination coverage, universal infant vaccination with conjugated pneumococcal vaccine (PCV) has significantly decreased the incidence of vaccine type nasopharyngeal carriage and invasive pneumococcal disease. The aim of this study is to examine immunization coverage rate and timely administration of the recently introduced PCV and compare to the established diphtheria-tetanus-acellular pertussis vaccine (DTaP) with similar schedule., Methods: A stratified random sample of healthy infants and children 6-36 months of age were recruited. Demographic data were collected from parents. Among enrolled children, immunization status for DTaP and PCV was noted from the child's health booklet., Results: Of 1105 children enrolled in the study, 586 (53%) were vaccinated in the private sector and the rest in the public sector. A significant higher proportion of children vaccinated at the private sector were fully vaccinated for PCV (71% versus 58%, p < 0.05) while no difference in the DTaP coverage was observed. Conversely, the compliance to the recommended vaccination schedule was much higher in the public sector for the first and second dose of PCV and second dose of DTaP. The overall, timely administration was higher for the DTaP vaccine when compared to PCV (p < 0.05). Moreover, adherence to the program was higher for the firstborn child of the family while significant differences were observed between different geographic regions. Interestingly, co-administration of DTaP and PCV was observed in only 2% of the children., Conclusion: In children residing in Cyprus, vaccination coverage and adherence to PCV vaccination schedule are significantly lower compared to the established DTaP vaccine. There is an urgent need for increasing the overall vaccination coverage as well as improving the adherence to vaccination schedule. Possible interventions are proposed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: This is an update of a Cochrane Review first published in 2015. The conclusions have not changed.Hypodermic needles of different sizes (gauges and lengths) can be used for vaccination procedures. The gauge (G) refers to the outside diameter of the needle tubing. The higher the gauge number, the smaller the diameter of the needle (e.g. a 23 G needle is 0.6 mm in diameter, whereas a 25 G needle is 0.5 mm in diameter). Many vaccines are recommended for injection into muscle (intramuscularly), although some are delivered subcutaneously (under the skin) and intradermally (into skin). Choosing an appropriate length and gauge of a needle may be important to ensure that a vaccine is delivered to the appropriate site and produces the maximum immune response while causing the least possible harm. Guidelines conflict regarding the sizes of needles that should be used for vaccinating children and adolescents., Objectives: To assess the effects of using needles of different sizes for administering vaccines to children and adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an immune response), procedural pain, and other reactogenicity events (adverse events following vaccine administration)., Search Methods: We updated our searches of CENTRAL, MEDLINE, Embase, and CINAHL to October 2017. We also searched proceedings of vaccine conferences and two trials registers., Selection Criteria: Randomised controlled trials evaluating the effects of using hypodermic needles of any gauge or length to administer any type of vaccine to people aged from birth to 24 years., Data Collection and Analysis: Three review authors independently extracted trial data and assessed the risk of bias. We contacted trial authors for additional information. We rated the quality of evidence using the GRADE system., Main Results: We included five trials involving 1350 participants in the original review. The updated review identified no new trials. The evidence from two small trials (one trial including infants and one including adolescents) was insufficient to allow any definitive statements to be made about the effects of the needles evaluated in the trials on vaccine immunogenicity and reactogenicity.The remaining three trials (1135 participants) contributed data to comparisons between 25 G 25 mm, 23 G 25 mm, and 25 G 16 mm needles. These trials included infants predominantly aged from two to six months undergoing intramuscular vaccination in the anterolateral thigh using the World Health Organization (WHO) injection technique (skin stretched flat, needle inserted at a 90° angle and up to the needle hub in healthy infants). The vaccines administered were combination vaccines containing diphtheria, tetanus, and whole-cell pertussis antigens (DTwP). In some trials, the vaccines also contained Haemophilus influenzae type b (DTwP-Hib) and hepatitis B (DTwP-Hib-Hep B) antigen components.Primary outcomesIncidence of vaccine-preventable diseases: No trials reported this outcome.Procedural pain and crying: Using a wider gauge 23 G 25 mm needle may slightly reduce procedural pain (low-quality evidence) and probably leads to a slight reduction in the duration of crying time immediately after vaccination (moderate-quality evidence) compared with a narrower gauge 25 G 25 mm needle (one trial, 320 participants). The effects are probably not large enough to be clinically relevant.Secondary outcomesImmune response: There is probably little or no difference in immune response, defined in terms of the proportion of seroprotected infants, between use of 25 G 25 mm, 23 G 25 mm, or 25 G 16 mm needles to administer a series of three doses of a DTwP-Hib vaccine at ages two, three, and four months (moderate-quality evidence, one trial, numbers of participants in analyses range from 309 to 402. The immune response to the pertussis antigen was not measured).Severe and non-severe local reactions: 25 mm needles (either 25 G or 23 G) probably lead to fewer severe and non-severe local reactions after DTwP-Hib vaccination compared with 25 G 16 mm needles (moderate-quality evidence, one trial, 447 to 458 participants in analyses). We estimate that one fewer infant will experience a severe local reaction (extensive redness and swelling) after the first vaccine dose for every 25 infants vaccinated with the longer rather than the shorter needle (number needed to treat for an additional beneficial outcome (NNTB) with a 25 G 25 mm needle: 25 (95% confidence interval (CI) 15 to 100); NNTB with a 23 G 25 mm needle: 25 (95% CI 17 to 100)). We estimate that one fewer infant will experience a non-severe local reaction (any redness, swelling, tenderness, or hardness (composite outcome)) at 24 hours after the first vaccine dose for every 5 or 6 infants vaccinated with a 25 mm rather than a 16 mm needle (NNTB with a 25 G 25 mm needle: 5 (95% CI 4 to 10); NNTB with a 23 G 25 mm needle: 6 (95% CI 4 to 13)). The results are similar after the second and third vaccine doses.Using a narrow gauge 25 G 25 mm needle may produce a small reduction in the incidence of local reactions after each dose of a DTwP vaccine compared with a wider gauge 23 G 25 mm needle, but the effect estimates are imprecise (low-quality evidence, two trials, 100 to 459 participants in analyses).Systemic reactions: The comparative effects of 23 G 25 mm, 25 G 25 mm, and 25 G 16 mm needles on the incidence of postvaccination fever and other systemic events such as drowsiness, loss of appetite, and vomiting are uncertain due to the very low quality of the evidence., Authors' Conclusions: Using 25 mm needles (either 23 G or 25 G) for intramuscular vaccination procedures in the anterolateral thigh of infants using the WHO injection technique probably reduces the occurrence of local reactions while achieving a comparable immune response to 25 G 16 mm needles. These findings are applicable to healthy infants aged two to six months receiving combination DTwP vaccines with a reactogenic whole-cell pertussis antigen component. These vaccines are predominantly used in low- and middle-income countries. The applicability of the findings to vaccines with acellular pertussis components and other vaccines with different reactogenicity profiles is uncertain.

Background: Routine influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccination of pregnant women to prevent poor maternal, fetal and neonatal outcomes is recommended practice; however, actual rates of influenza vaccine acceptance are typically well below the (Healthy People 2020, 2015) goal of 80%., Objective: We sought to identify barriers to accepting either vaccination., Materials and Methods: From December 2014 to April 2015 women were given a questionnaire eliciting their experiences, attitudes and history of influenza and Tdap vaccination in pregnancy during their routine prenatal care appointments at a tertiary care center. Patient demographics were included in the questionnaire. A similar questionnaire was administered to prenatal care providers. Patient influenza and Tdap vaccination acceptance rates were compared and predictors of vaccine acceptance were analyzed with bivariate logistic regression., Results: Out of the 400 patient questionnaires distributed, 338 (84.5%) were completed and returned; 24 of 45 (53.3%) provider questionnaires were returned. Vaccination acceptance rates were 70.7% for the influenza vaccine and 76.3% for the Tdap vaccine. The logistic regression model indicated that predictors of acceptance for either vaccine in pregnancy are patient attitude and previous vaccination history. Patient attitudes were more favorable towards Tdap than influenza vaccination. The combination of healthcare provider recommendation and educational materials was significantly predictive of both Tdap and influenza vaccine acceptance. The most common reasons given for declining the influenza vaccine were safety concerns; the most common reasons given for declining the Tdap vaccine were that patients did not think it was required again when they received the vaccine before pregnancy., Conclusions: Our study suggests that providers can improve Tdap and influenza vaccination acceptance in pregnancy by recommending the vaccination in combination with provision of educational materials on the vaccines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Low adult vaccination coverage in Indonesia may contribute to a recent outbreak of diphtheria in Indonesia. Although well known as a pediatric vaccine, diphtheria vaccination should be administered as booster to adolescence and adults for longer prevention. Adult vaccine differs from pediatric vaccine but have similar protection. Additionally, there is special recommendation to vaccinate pregnant women and elderly people aged 65 years or more.

Background: In Nigeria and many parts of the world, the pentavalent vaccine is replacing the diphtheria-pertussis-tetanus (DPT) vaccine in tetanus prevention., Aims and Objectives: The aim of this study was to compare the anti-tetanus immunoglobulin G (IgG) response of children who received DPT with those who received the pentavalent vaccine., Subjects and Methods: A cross-sectional survey of anti-tetanus IgG levels in children aged 6 months to 5 years who received DPT and in children who received the pentavalent vaccine. IgG antibody levels were determined using enzyme-linked immunosorbent assay. The protective level was set at ≥0.1 IU/ml., Results: One hundred and twenty-two out of 130 children (93.9%) who had received DPT had protective levels of anti-tetanus IgG compared to 278 out of 288 children (96.5%) who had received the pentavalent vaccine. The difference was not statistically significant (P = 0.21). The median IgG antibody level in those who received DPT was 1.1 IU/ml (interquartile range (IQR) 0.4-1.8) compared with 0.6 IU/ml (IQR 0.4-1.4) in those who received pentavalent vaccine (P = 0.006), with age being the only predictor of variability in the multivariate analysis., Conclusion/recommendation: DPT and pentavalent vaccines are equally effective in inducing protective levels of anti-tetanus IgG in children. Vaccination with the pentavalent vaccine, which is the current policy in Nigeria and many other parts of the world, should continue., Competing Interests: There are no conflicts of interest

Background: Patients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients., Aims: The aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster., Methods: We performed a cross-sectional study evaluating antibody responses to Tdap vaccine among IBD patients compared to HC. Our study consisted of three patient groups: adults with IBD stratified by maintenance medication regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3) combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate))., Results: Ninety IBD patients and 20 HC participated. Pertussis pertactin antibody concentrations were significantly lower in IBD patients (p = 0.021) compared to HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to those on thiopurine monotherapy (p = 0.028). Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001), and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to the thiopurine monotherapy group (p < 0.001)., Conclusion: IBD patients on anti-TNF agents had lower antibody concentrations to diphtheria and pertussis. These findings suggest a need for different Tdap booster schedules for IBD patients on anti-TNF therapy. Clinical Trials Registry NCT02434133.

Aim: To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV B ) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV)., Methods: This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV B or dTap-IPV R ) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated., Results: 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV B group and 130 in the dTap-IPV R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV B group., Conclusion: Non-inferiority of dTap-IPV B to dTap-IPV R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old., Trial Registration: NCT01245049 (ClinicalTrials.gov)., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In May 2015, following a 30-year diphtheria-free interval in Catalonia, an unvaccinated 6-year-old child was diagnosed with diphtheria caused by toxigenic Corynebacterium diphtheriae . After a difficult search for equine-derived diphtheria antitoxin (DAT), the child received the DAT 4 days later but died at the end of June. Two hundred and seventeen contacts were identified in relation to the index case, and their vaccination statuses were analysed, updated and completed. Of these, 140 contacts underwent physical examination and throat swabs were taken from them for analysis. Results were positive for toxigenic C. diphtheriae in 10 contacts; nine were asymptomatic vaccinated children who had been in contact with the index case and one was a parent of one of the nine children. Active surveillance of the 217 contacts was initiated by healthcare workers from hospitals and primary healthcare centres, together with public health epidemiological support. Lack of availability of DAT was an issue in our case. Such lack could be circumvented by the implementation of an international fast-track procedure to obtain it in a timely manner. Maintaining primary vaccination coverage for children and increasing booster-dose immunisation against diphtheria in the adult population is of key importance.

Background: Over the years, diphtheria was known as contagious fatal infection caused by Corynebacterium diphtheria that affects upper respiratory system. The spread of diphtheria epidemic disease is best prevented by vaccination with diphtheria toxoid vaccine. Aluminum adjuvants were reported to stimulate the immune responses to killed and subunit vaccines., Objective: Our study aimed to minimize adjuvant particles size, to gain insight of resulting immunity titer and impact on immune response antibody subtypes., Methods: Aluminum salts and calcium phosphate adjuvants were prepared, followed by micro/nanoparticle adjuvants preparation. After formulation of diphtheria vaccine from diphtheria toxoid and developed adjuvants, we evaluated efficacy of these prepared vaccines based on their impact on immune response via measuring antibodies titer, antibodies isotyping and cytokines profile in immunized mice., Results: A noteworthy increase in immunological parameters was observed; antibodies titer was higher in serum of mice injected with nanoparticle adjuvants-containing vaccine than mice injected with standard adjuvant-containing vaccine and commercial vaccine. Aluminum compounds adjuvants (nanoparticles and microparticles formulation) and microparticles calcium phosphate adjuvant induce TH2 response, while nanoparticles calcium phosphate and microparticles aluminum compounds adjuvants stimulate TH1 response., Conclusions: Different treatments to our adjuvant preparations (nanoparticles and microparticles formulation) had a considerable impact on vaccine immunogenicity.

Vaccines based on pathogen components require adjuvants to enhance the antigen-specific adaptive immune response. Intramuscular injection of adjuvanted-vaccines induces inflammatory cytokines and inflammatory nodules at the injection site within 48 hr after injection (Vaccine 2014; 32: 3393-401). In the present study, long-term regulation of cytokine production was investigated at 3, 6, 24, and 48 hr, 5 and 7 days, and 2 and 4 weeks after immunization with human papilloma virus (HPV), diphtheria and tetanus toxoids combined with acellular pertussis (DTaP), Haemophilus influenza type B (Hib), and pneumococcal conjugated (PCV) vaccines in mouse models. The second dose was given 4 weeks later, and cytokine profiles were investigated 2, 5, and 7 days after re-immunization. IL-1β, IL-6, granulocyte-colony stimulating factor (G-CSF), and MCP-1 were produced from 3 hr and peaked at 48 hr after immunization with Cervarix in mice. IL-4, MCP-1, and TNF-α peaked at 5 or 7 days after immunization with Gardasil. These cytokines decreased 7 days after immunization with Cervarix and Gardasil. After the second dose, similar responses were observed. Both vaccines induced neutrophil extracellular traps (NET) in inflammatory nodules. The peak amount of IL-1β, IL-6, G-CSF, and MCP-1 was observed on day 5 of immunization and that of IL-4 on days 5-7 of immunization with DTaP, but no increase in IL-6 and G-CSF was observed after re-immunization. A similar response was noted after immunization with PCV13. An inflammatory response is essential for the development of adaptive immunity through the production of inflammatory cytokines., (© 2017 The Societies and John Wiley & Sons Australia, Ltd.)

Pertussis is a highly contagious disease, for which periodic peaks in incidence and an increasing number of outbreaks have been observed over the last decades. The reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine (Tdap) can be used to boost individuals aged ≥10 years, vaccinated in infancy with a diphtheria-tetanus-acellular pertussis vaccine (DTaP), to reduce pertussis morbidity and maintain protection against diphtheria and tetanus throughout adolescence and adulthood. This phase III, open-label, non-randomized, multicenter follow-up study (NCT01738477) enrolled 19-30-year-old participants from the United States who had received booster vaccination 10 years earlier with either Tdap (Tdap group) or Td (Td group). In total, 128 (Tdap group) and 37 (Td group) participants received Tdap vaccination. After administration of Tdap, all participants were seroprotected (antibody concentrations ≥0.1 international units [IU]/ml) against diphtheria and tetanus. Immune responses to a second Tdap dose in the Tdap group were shown to be non-inferior to responses elicited by a first Tdap dose in the Td group for diphtheria and tetanus and to a 3-dose DTaP vaccination during infancy for pertussis antigens (primary objectives). Post-booster vaccination, all participants in both groups had antibody concentrations above assay cut-offs and antibody geometric mean concentrations increased by 3.8-15.5-fold compared to pre-booster levels for all antigens. The incidence of adverse events was similar in the Td (80.6%) and Tdap (85.6%) groups (no serious adverse events reported). A Tdap dose administered after previous Td or Tdap vaccination was shown to be immunogenic and well-tolerated in young adults, supporting repeated vaccination with Tdap at 10-year intervals.

Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.