Diphtheria Toxoid Research Articles

Evaluation of IgG antibody response to diphtheria toxin one month after tetanusdiphtheria vaccination among 7-years-old children in a mountainous district in the Northern region of Viet Nam in 2020

Under the outbreak of diphtheria disease mostly among preschool and primary school children, following the recommendations of WHO, Vietnam has implemented a second booster dose of diphtheria vaccine since 2019 for children at 7 years old in some at-risk provinces. This study evaluated the IgG antibody response to diphtheria toxid in a group of 7-year-old children living in Tran Yen district, Yen Bai province, after receiving one dose of Tetanus-diphtheria (Td) vaccine with reduced diphtheria toxoid in 2020. The study involved community intervention, monitoring 98 7 yearold children who received the Td vaccine to compare the proportion of children with a full protective antibody level (antibody concentration ≥ 0.1IU/mL) before and one month after vaccination. The results showed that the proportion of children with a protective antibody level against diphtheria toxin increased from 35% to 95% one month after vaccination. The intervention coefficient was 171%. 80% of children achieved long-term protective antibody levels (≥ 1.0IU/mL). The Td vaccine helped children achieve full and long-term protective antibody levels, even in those without the complete primary vaccination series and those with only baseline or no protection levels. Vaccinating 7-year-old children in areas with limited vaccination coverage and no actual circulating diphtheria cases is effective and necessary to prevent disease outbreaks. The study’s results suggest the Ministry of Health should consider including the Td vaccine in the Expanded Immunization Program for regular vaccination for 7-year-old children instead of approving current annual plans.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

Adherence to Advisory Committee on Immunization Practices in diabetes mellitus patients in Saudi Arabia: A multicenter retrospective study.

Patients with diabetes mellitus (DM) are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications. The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices (CDC/ACIP) issued immunization re-commendations to protect this patient population. To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate. An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey. Among participants, 10.01% (n = 71) had never received any vaccine, while 85.89% (n = 609) received at least one dose of the coronavirus disease 2019 (COVID-19) vaccine, and 34.83% (n = 247) had received the annual influenza vaccine. Only 2.96% (n = 21), 2.11% (n = 15), and 1.12% (n = 8) received herpes zoster, tetanus, diphtheria, and pertussis (Tdap), and human papillomavirus (HPV) vaccines, respectively. For patients with DM in Saudi Arabia, the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster, Tdap, pneumococcal, and HPV. Factors such as vaccine recommendations provided by family physicians or specialists, site of care, income level, DM-related hospitalization history, residency site, hemoglobin A1c (HbA1c) level, and health sector type can significantly influence the vaccination rate in patients with DM. Among non-vaccinated patients with DM, the most reported barriers were lack of knowledge and fear of side effects. This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM. In Saudi Arabia, patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster, Tdap, pneumococcal, and HPV. Factors such as vaccine recommendations provided by family physicians or specialists, the site of care, income level, DM-related hospitalization history, residency site, HbA1c level, and health sector type can significantly influence the vaccination rate in patients with DM.

Signatures of neurological adverse events after vaccination

There have been reports associated with the development of neurological adverse events (AEs) post-vaccination. Here, we retrospectively examine the Vaccine Adverse Events Reporting System (VAERS) database for neurological AEs reported following vaccination. Since VAERS is a passive reporting system, to minimize reporting bias and to reduce background events, this retrospective study examines both age-stratified AE reports made with onset within 24 h of immunization, and age-stratified AE reports regardless of timeframe from immunization. Immediate temporal onset data patterns for febrile convulsion, seizure, and syncope AEs were observed for multiple vaccines. For age-stratified AEs in infants up to 3 years of age, the following patterns of high association were observed: (i) Aphasia, autism spectrum disorder, and speech disorder were found to be highly associated with the measles, mumps, and rubella and hepatitis B (HepB) vaccines; (ii) febrile convulsion and syncope were found to be highly associated with the meningococcal group B vaccine; and (iii) seizures were found to be highly associated with diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccines.

Re-emergence of Diphtheria. A Case Report in a Pediatric Emergency at a Tertiary Care Hospital in Karachi

Diphtheria, caused by Corynebacterium diphtheria, is an acute bacterial infection that primarily affects the respiratory system. With the availability of diphtheria vaccines, the incidence of the disease has significantly decreased globally. However, in recent times, there has been a concerning resurgence of diphtheria in various parts of the world, including Pakistan, and hence presents a unique and pressing public health challenge, as evidenced by our case study exclusively reported from the pediatric emergency department. The study highlights the importance of early recognition and management of diphtheria cases and the need for booster doses in the EPI program to prevent this deadly disease re-emergence.

Pharmacists’ role in maternal immunization

Maternal immunization is an important strategy to safeguard infants against vaccine-preventable diseases such as pertussis, which poses a significant economic burden on the health care system. Although the Tetanus, Diphtheria, and Pertussis vaccine has been recommended for pregnant individuals since 2018, uptake varies widely across Canadian provinces. As 4.5 million Canadians do not have access to a regular physician, there is a need to find alternate ways of informing pregnant individuals about maternal immunization schedules. Given the wide accessibility of pharmacists across Canada, they should have a leading role in informing pregnant individuals about maternal vaccines. Training guidelines for pharmacists would ensure informative and effective conversations about vaccinations and promote vaccine safety and benefits, facilitating administration. Increased participation from pharmacists can significantly contribute to improving maternal and child health outcomes, with the goal of reducing the burden of vaccine-preventable diseases in Canada.

The Influence of CD4+ T-Lymphocytes on the Strength of Anti-Diphtheria Immunity in Adult People Living with HIV

The Influence of CD4+ T-Lymphocytes on the Strength of Anti-Diphtheria Immunity in Adult People Living with HIV

Clinical spectrum and outcomes of the 2019-2020 pediatric diphtheria outbreak in Yemen

Background Diphtheria is an acute bacterial infectious disease characterized by serious morbidity and mortality. Outbreaks continue to occur in developing countries despite national vaccination programs. Vaccination, early recognition the disease, and adequate intervention are needed to avoid devastating outcomes.
 Objective To describe the clinical spectrum of childhood diphtheria and its association to outcomes during the 2019-2020 diphtheria outberak in Yemen.
 Methods This was a retrospective study to assess the demographic, clinical features, and outcomes of paediatric respiratory diphtheria in patients with diphtheria during the outbreak from September 2019 until May 2020 admitted at Mukalla Maternity and Children Hospital. We used SPSS 22 version for data analysis.
 Results There were 34 culture-confirmed diphtheria cases included in this study, their age ranged from 13 months to 15 years old. Most of the cases (76.5%) happened to children at more than 5 years old. There was no gender difference. Of these 34-positive diphtheria, 79.4% from Hadramout and 17.6% from Shabwa governorate. Most of the cases (35.3%) were admitted in December. More than half of the patients (52.9%) were unimmunized. Fever, sore throat, and enlarged tonsils were presented in all patients, dysphagia (82.4 %), pseudomembrane (91.7%), bull neck (52.9%), and stridor (8.8%) were also found in some patients. Complications included acute renal failure (20.6%), disseminated intravascular coagulation (DIC), shock (17.6%), and myocarditis (8.8%). Significant poor outcome (P< 0.05) was associated with bull neck, myocarditis, acute renal failure, DIC, and shock. The case fatality rate (CFR) was 20.6%.
 Conclusion Fever, sore throat, tonsillitis, pseudomembrane, and bull neck are high index suspicion of diphtheria and anticipation of ominous outcome. The shifting of occurrence of diphtheria to older age group indicates the need for booster(s) diphtheria toxoid vaccine in addition to improving and strengthening the current immunization program.

Has COVID-19 Affected DTP3 Vaccination in the Americas?

In the Americas, deaths by diseases avoidable with vaccines are a significant contributor to child mortality. An essential means of reducing this is through broad vaccine coverage. The COVID-19 pandemic has posed a potential disruption to vaccine coverage due to its effects on the healthcare system. this study aims to evaluate the impact of the COVID-19 pandemic on DTP3 vaccination coverage in the Americas, investigating trends from 2012 to 2022 to identify significant changes, regional disparities, and the overall effect of the pandemic on progress towards global immunization targets. This study used the coverage data for the third dose of the diphtheria, tetanus, and pertussis vaccine (DTP3) pulled from UNICEF databases spanning 2012 to 2022. We conducted a Joinpoint regression to identify points of significant trend changes. The annual percentage change (APC) and 95% confidence intervals (95% CIs) were calculated for America and its regions. We also used segmented regression analysis. Using the Chi-square test, we compared DTP3 vaccination coverage for each country between 2019 and 2022. Overall, America saw a decrease in vaccine coverage during this period, with an APC of -1.4 (95% CI -1.8; -1.0). This trend varied across regions. In North America, the decrease was negligible (-0.1% APC). South America showed the steepest decrease, with an APC of -2.5%. Central America also declined, with an APC of -1.3%. Our findings suggest a concerning trend of declining DTP-vaccination rates in the Americas, exacerbated in certain regions, in the wake of the COVID-19 pandemic. The absolute decrease in vaccine coverage in the Americas was -4% between 2019 and 2022, with the most important drop being in Central America (-7%). However, six countries reported increased vaccination rates post-COVID-19, led by Brazil, with a 7% increase. Conversely, twenty-two countries registered a decline in DTP3 vaccine coverage, with the average decrease being -7.37%. This decline poses an important challenge to achieving the WHO's target of 90% coverage for the third dose of DTP by 2030, as evidenced by the reduction in the number of countries meeting this target from 2019 to 2022. The COVID-19 pandemic has impacted vaccine coverage in America, leading to a decrease, especially across Central America.

Comparative Evaluation of Recombinant and Acellular Pertussis Vaccines in a Murine Model.

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

Safety and immunogenicity of conjugate vaccine for typhoid (Vi-DT): Finding from an observer-blind, active-controlled, randomized, non-inferiority, phase III clinical trial among healthy volunteers

ABSTRACT Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D. Group A, B, and C received 25 μg (0.5 mL) of Vi-DT study vaccine and participants in Group D received 25 μg (0.5 mL) Vi-TT vaccine. We descriptively analyzed safety in all the participants receiving one dose of the investigational vaccine. The anti-Vi-IgG seroconversion rate in Vi-DT recipients was 99.71% (97.5% CI 98.04–99.96; 344 of 345 participants) and 99.13% (94.27–99.87; 114 of 115) in Vi-TT recipients which indicates that Vi-DT vaccine is non-inferior to Vi-TT vaccine. In safety aspect, 16.81% of total subject had at least one solicited adverse reaction and 22.61% of the Vi-TT participants experienced at least one solicited adverse reaction with most of them being local adverse reactions. None of the enrolled participants reported serious adverse events. Our study shows that a single dose of the Vi-DT vaccine is immunogenic, safe to administer and non-inferior to the Vi-TT vaccine four weeks after vaccination.

Safety and immunogenicity of an indigenously developed tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine (Tdap) in adults, adolescents, and children in India

ABSTRACTBackgroundThis study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)’s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster vaccine (Tdap).Research Design and MethodsIn this Phase II/III, multicenter, randomized, active-controlled, open-label study, 1500 healthy individuals, aged 4–65 years, were randomized to receive a single dose of SIIPL Tdap or comparator Tdap vaccine (Boostrix®; GlaxoSmithKlines, India). Adverse events (AEs) during initial 30 minutes, 7-day, 30-day post-vaccination were assessed. Blood samples were taken before and 30 days post-vaccination for immunogenicity assessment.ResultsNo significant differences in incidence of local and systemic solicited AEs were observed between the two groups; no vaccine-related serious AEs were reported. SIIPL Tdap was non-inferior to comparator Tdap in achieving booster responses to TT and DT in 75.2% and 70.8% of the participants, respectively, and to pertussis toxoid (PT), pertactin (PRN), and filamentous hemagglutinin (FHA) in 94.3%, 92.6%, and 95.0% of the participants, respectively. Anti-PT, anti-PRN, and anti-FHA antibody geometric mean titers in both the groups, were significantly higher post-vaccination compared to pre-vaccination.ConclusionsBooster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to immunogenicity against tetanus, diphtheria, and pertussis and was well tolerated.

Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion Maternal Vaccine Coadministered With Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study.

Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12-18 months after first vaccination. The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination. This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used. NCT04138056.

COMPLEXATION OF CURCUMIN WITH BOVINE SERUM ALBUMIN AND DIPHTHERIA TOXOID CRM197

Aim. The goal of the study is to demonstrate the binding sites for curcumin on the protein carriers - bovine serum albumin and diphtheria toxoid CRM197. BSA was chosen as a potential non-specific protein carrier because of its widely used in medicine as a drug carrier. Methods. In the investigation, both spectrophotometric and molecular docking methods were used. Results. Two stable binding sites were demonstrated for BSA to bind curcumin. CRM197 was taken as a well-studied carrier protein with its own antitumor activity and has been investigated as a specific carrier with a high affinity for cancer cells with overexpression of epidermal growth factor receptor. Our results showed one possible curcumin binding site, making CRM197 an ideal specific curcumin delivery platform that provides at least an additive effect in anticancer therapies. Conclusions. In conclusion, both studied proteins form stable complexes with curcumin that can lay in base of the commercial drug application.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines

IntroductionRecombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. MethodsThis is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. ResultsAnti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5gen group at birth (118.8 [95% CI 93.9–150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (2.6 [1.7–4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. ConclusionsBioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.

The rise of the throat distemper.

Diphtheria vaccination in the EPI program has controlled much of the childhood infection. Nevertheless, sporadic adult cases of Diphtheria come up every now and then in Pakistan and other South-Asian countries. This is, most likely, due to the lack of booster dosing of Diphtheria vaccine in adulthood. In an effort to suppress the spread of this infection, adult vaccinations need to be mandated.

Development of a composite scoring system to rank communities at high risk of zero-dose children in Cameroon: A geospatial analysis.

Despite growing efforts to improve access to vaccination, millions of children, especially in developing countries, have not received a single dose of diphtheria, tetanus, and pertussis (DTP) vaccine. Consequently, they are often called zero-dose children (ZDC). With limited health resources, prioritising communities for rapid and mass zero-dose catch-up vaccination in missed communities to avert epidemic outbreaks is complicated by unreliable denominators used to compute vaccination coverages. Incorporating other indicators of access and utilisation of vaccination services can help with identifying and ranking missed communities based on the likelihood of finding ZDC. We described the process of generating a scoring method to rank health areas in Cameroon based on their likelihood of containing ZDC. We used geospatial analysis to compute and aggregate health area characteristics, including hard-to-reach (HTR) areas (defined as areas of settlement above a one- (for urban areas) or 15-kilometre radius (for rural areas) beyond a vaccinating health facility), amount of area covered by slums and new area settlement, and percentage of children unvaccinated for DTP-1. We attributed a weight based on the ability to limit accessibility or utilisation of vaccination services to each characteristic and computed the score as a weighted average of health area characteristics. The health area score ranged from 0 to 1, with higher scores representing a higher likelihood of containing ZDC. We stratified the analysis by rural and urban health areas. We observed substantial district and regional variations in health area scores, with hotspots health areas (administrative level 4) observed in the Far North (0.83), North (0.81), Adamawa (0.80), East (0.75), and South West (0.67) regions. The Adamawa region had the highest percentage of health areas with the highest score (78%), followed by the East (50%), West (48%), and North (46%) regions. For most regions (Far North, South, South West, Littoral, West, and North West), DTP-1 contributed the most to the score. However, HTR settlement areas within a health area contributed substantially to the overall score in the East, North, and Adamawa regions. We found substantial variations in health area scores with hotspots in the Far North, North, Adamawa, East, and South West regions. Although DTP-1 could be used as an indicator to identify health areas with ZDC for most communities, HTR settlement area was a valuable indicator in ranking priority health areas in the East, North, and Adamawa regions, further emphasising the need to consider other indicators before prioritisation.

A deterministic mathematical model for optimal control of diphtheria disease with booster vaccination

Diphtheria is an infectious disease caused by a strain of Corynebacterium diphtheria and forms part of the childhood vaccine-preventable diseases. The Diphtheria vaccine is a component of one of the routine vaccines given to children thrice before their first birthday. The protection against diphtheria derived from the diphtheria vaccine in infancy wanes in later childhood, necessitating a booster dose to protect the child as they grow older. To determine the impact of a booster dose of the diphtheria vaccine amidst a contaminated environment, a diphtheria model that incorporates a vaccine booster and a contaminated environment is formulated. The reproduction number R0 is computed and used to prove the local and global stability of the disease-free equilibrium. Global sensitivity analysis is conducted via the application of Latin Hypercube Sampling (LHS) with a Partial Rank Correlation coefficient on the infected humans and the contaminated environment to deduce the most sensitive parameters of the dynamics of diphtheria disease. Then, the model is further extended based on the result of the global sensitivity analysis by introducing four time-dependent controls, disinfection, screening/treatment, booster vaccination, and hygiene practice, to form an optimal control model. The control model is analyzed using Pontryagin’s maximum principle. The numerical simulation shows that diphtheria disease will reduce drastically in the community if any control combination involves booster vaccination since the diphtheria vaccine in infancy wanes after ten years. In a situation where there are limited resources to implement all the controls simultaneously, it is recommended to implement any two of the combined controls: disinfection of the environment and administration of booster vaccination or screening/treatment of the asymptomatic infected and administration of booster vaccination. The study shows that the best combination is to disinfect the environment, screen/treat the asymptomatic infected humans, and administer booster vaccination to the community.

Evaluation of Biodegradable Microparticles for Mucosal Vaccination Against Diphtheria Toxoid: Nasal Efficacy Studies in Guinea Pigs.

In this study, poly-(ɛ-caprolactone) (PCL) and poly-(lactic-co-glycolic acid) (PLGA) microparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. Antigen-containing microparticles were prepared using the double emulsion (w/o/w) solvent evaporation method. The average geometric diameter of the particles was found to be between 7 and 24 µm, which is suitable for uptake by the antigen-presenting cells in the nasal mucosa. Although the differences were insignificant, the PLGA polymer-containing formulations exhibited the highest encapsulation efficiency. Microparticle formulations, prepared with both PLGA and PCL polymers, were successfully produced at high production yields. The in vitro release profile was presented as a biexponential process with an initial burst effect due to the release of the protein adsorbed on the microsphere surface, and the subsequent sustained release profile is the result of protein diffusion through the channels or pores formed in the polymer matrix. DT-loaded microparticles, DT solution in phosphate-buffered saline (PBS), and empty microparticles (control) were administered via nasal route and subcutaneously to guinea pigs. The antibody content of each serum sample was determined using an enzyme-linked immunosorbent assay (ELISA). Absorbance values of the ELISA test showed that PLGA- and PCL-bearing microparticles could stimulate an adequate systemic immune response with intranasal vaccination. In addition, PLGA and PCL microparticles resulted in significantly increased IgG titers with intranasal administration as a booster dose following subcutaneous administration. PCL polymer elicited a high immune response compared with PLGA polymer (p <0.05).

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies.

Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an in silico prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient's anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.