Diphtheria Toxoid Research Articles

The Impact of the U.S. Maternal Tdap Vaccination Program on Preventing Pertussis in Infants 2-<6 Months of Age: A Case-control Evaluation

Abstract Background To protect infants aged <2 months against pertussis, the United States recommends Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during each pregnancy. Data are limited on the strategy’s effectiveness against pertussis in infants aged ≥2 months. Methods Pertussis cases aged 2-<6 months with cough onset between 1/1/2011-12/31/2014 were identified in six U.S. states. Controls were 2-<6 months of age, hospital-matched, and selected by birth certificate. Mothers were interviewed to collect demographic and healthcare information. Provider-verified vaccination history was obtained for infants and mothers. Adjusted odds ratios (aORs) were calculated using conditional logistic regression; overall vaccine effectiveness (VE) was estimated as (1 - aOR) x 100. To describe maternal Tdap VE modified by infant DTaP (diphtheria and tetanus toxoids, and acellular pertussis) doses, case-control sets were unmatched and a time-to-event analysis conducted through a Generalized Linear Mixed Model. Results A total of 335 cases and 927 controls were enrolled. The overall adjusted VE estimate for Tdap during pregnancy was 45.6% (95% confidence interval [CI], 5.8% – 68.5%) and increased slightly, but not significantly against infant hospitalization (55.7% (-116.8% – 90.9%)). Although point estimates were not significant, VE was modified by infant DTaP doses (58.8% (-6.0% – 84.0%) for zero DTaP doses, 30.5% (-21.4% – 60.2%) for one DTaP dose, and 3.2% (-170.8% – 65.4%) for two DTaP doses). Conclusions Our study suggests that there is some benefit of maternal Tdap vaccination beyond the first two months of life, however, on-time vaccination of infants remains critical to maintain protection from pertussis.

Analytical Challenges in Novel Pentavalent Meningococcal Conjugate Vaccine (A, C, Y, W, X)

Multivalent meningococcal conjugate vaccines are a significant focus for the scientific community in light of the WHO’s mission to defeat meningitidis by 2030. Well-known meningococcal vaccines such as MenAfriVac, Nimenrix, Menveo, and MenQuadfi are licensed in various parts of the world and have been successful. Recently, the World Health Organization (WHO) qualified MenFive (meningococcal A, C, Y, W, and X) conjugate vaccine, further enhancing the battery of vaccines against meningitis. The antigenic nature of the current and new serogroups, the selection of carrier proteins, and the optimal formulation of these biomolecules are pivotal parameters for determining whether a biological preparation qualifies as a vaccine candidate. Creating appropriate quality control analytical tools for a complex biological formulation is challenging. A scoping review aims to identify the main challenges and gaps in analyzing multivalent vaccines, especially in the case of novel serogroups, such as X, as the limited literature addresses these analytical challenges. In summary, the similarities in polysaccharide backbones between meningococcal serogroups (C, Y, W sharing a sialic backbone and A, X sharing a phosphorous backbone) along with various conjugation chemistries (such as CNBr activation, reductive amination, CDAP, CPIP, thioether bond formation, N-hydroxy succinimide activation, and carbodiimide-mediated coupling) resulting into a wide variety of polysaccharide -protein conjugates. The challenge in analyzing carrier proteins used in conjugation (such as diphtheria toxoid, tetanus toxoid, CRM diphtheria protein, and recombinant CRM) is assessing their purity (whether they are monomeric or polymeric in nature as well as their polydispersity). Additional analytical challenges include the impact of excipients, potential interference from serogroups, selection and establishment of standards, age-dependent behavior of biomolecules indicated by molecular size distributions, and process-driven variations. This article explains the analytical insights gained (polysaccharide content, free saccharide, free proteins, MSD) during the development of the MenFive vaccine and highlights the crucial gaps and challenges in testing.

Surveillance for adverse events following immunization in Hebei Province, China, 2018-2020

ABSTRACT The aim of this study was to analyze the incidence and characteristics of adverse events following immunization (AEFI) with post-licensure vaccines used in Hebei province from 2018 to 2020 and to evaluate the safety of vaccines. All information of AEFI was gained from national adverse event following immunization surveillance system (NAEFISS) in Hebei Province from 2018 to 2020. Descriptive epidemiology method was used to analyze the data about AEFI in Hebei province. Reporting rates of AEFI were calculated by sex, age, city, categories of AEFI, severity of AEFI, reaction categories, etc. A total of 35,999 AEFI were reported through NAEFISS, and the average annual rate was 47.64/100,000 doses. The reporting rates of common adverse reactions and rare adverse reactions were 46.37/100,000 doses and 1.05/100,000 doses. The male-to-female ratio was 1.26:1. Most of the AEFI were concentrated in the ≤1 year age group and were reported in the second quarter and third quarter. The majority of AEFI were reported to be recovered or improved, and about 62% of the AEFI occurred within 24 hours after vaccination. Vaccines associated with the highest reporting rate of AEFI were diphtheria, tetanus and acellular pertussis combined vaccine (DTaP, 170.45/100,000 doses). The reporting rate of allergic rash was found to be the highest in the adverse reactions (0.29/100,000 doses). The majority of AEFI cases were common adverse reactions, while serious rare adverse reactions caused by vaccines were extremely uncommon, and all vaccines used in Hebei Province were safe.

Routine vaccination coverage at ages 2 and 7, before, during, and after the COVID-19 pandemic: Results from the STARVAX surveillance system.

A decline in routine vaccination coverage in children has been observed after the onset of the COVID-19 pandemic, but it is unclear whether these declines were sustained over time. This analysis assessed changes in vaccination coverage at ages 2 and 7years for routinely administered vaccinations before, during, and after the COVID-19 pandemic. Vaccination coverage was measured using yearly data from the Standardized Reporting on Vaccination (STARVAX) surveillance system between December 31, 2019, and December 31, 2023. Four provinces (Alberta, Saskatchewan, Manitoba, and New Brunswick) and one territory (Yukon) produced reports from their immunization registries and provided the Public Health Agency of Canada with the numbers of vaccinated 2-year-old and 7-year-old children. Population estimates from Statistics Canada and the Yukon Bureau of Statistics were used as the denominators. There was a decline in vaccination coverage in 2023 compared to 2019. In 2-year-olds, coverage for one dose of the measles, mumps, and rubella (MMR) vaccine and four doses of the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine decreased from 89.5% to 82.5% and from 79.9% to 72.1%, respectively. Among 7-year-olds, DTaP (up-to-date) and MMR (two doses) vaccination coverage decreased from 77.1% to 68.8% and 86.3% to 75.6%, respectively. These declines are of concern and suggest that health care professionals should provide parents with accurate information regarding vaccines and encourage them to have their children vaccinated and keep vaccinations up to date.

Community-led diphtheria vaccination campaign to manage a diphtheria outbreak in a remote Aboriginal community.

In 2022, five cases of diphtheria were identified in and around Wujal Wujal, a discrete Aboriginal community in Far North Queensland. This prompted a mass diphtheria vaccination campaign in the community which increased the proportion of residents aged ≥ 14 years receiving a diphtheria containing vaccine in the prior twelve months from 5% to 74%. No further cases were detected in the subsequent twenty-two months.

Coverage with Selected Vaccines and Exemption Rates Among Children in Kindergarten - United States, 2023-24 School Year.

In the United States, states and local jurisdictions set vaccination requirements for school attendance, conditions and procedures for exemptions from these requirements, grace periods for submitting documentation, and provisional enrollment for students who need more time to be vaccinated. States annually report data to CDC on the number of children in kindergarten who meet, are exempt from, or are in the process of meeting requirements. Data reported by 49 states and the District of Columbia (DC) for the 2023-24 school year were used for national- and state-level estimates of the following measures: complete vaccination with required doses of measles, mumps, and rubella vaccine (MMR), diphtheria, tetanus, and acellular pertussis vaccine (DTaP), poliovirus vaccine (polio), and varicella vaccine (VAR); exemptions from vaccination; and school attendance while meeting requirements. The 2023-24 kindergarten class became age-eligible to complete most state-required vaccinations during the COVID-19 pandemic, after schools had returned to routine in-person learning. Compared with approximated national coverage levels across all reported vaccines for the 2019-20 (95%) and 2022-23 (93%) school years, coverage dropped below 93% for the 2023-24 school year, ranging from 92.3% for DTaP to 92.7% for MMR. Exemptions increased to 3.3%, compared with those during the 2022-23 (3.0%) and 2021-22 school years (2.6%). Coverage with MMR, DTaP, polio, and VAR decreased in 35, 32, 33, and 36 jurisdictions, respectively, compared with the 2022-23 school year. Exemptions increased in 41 jurisdictions, with 14 reporting that >5% of kindergartners had an exemption from one or more vaccine. Efforts by health departments, schools, and providers are needed to ensure that students begin school fully vaccinated.

Trends of Diphtheria–Tetanus–Pertussis and Measles Vaccine Coverage Preceding and during the COVID-19 Pandemic: An Analysis of the WHO European Region from 2000 to 2022

Available data highlights the significant impact of the COVID-19 pandemic on global vaccination trends. Despite this, comprehensive evaluations of these changes at the European level are still scarce. This study examines coverage for diphtheria, tetanus, and pertussis (DTP) and measles-containing vaccines (MCV) in the WHO European Region from 2000 to 2022. Vaccination coverage data, defined as the percentage of surviving infants who received the first and third doses of DTP (DTP1 and DTP3) and the first and second doses of MCV (MCV1 and MCV2), were extracted from UNICEF databases. Joinpoint regression analysis was employed to identify joinpoints in the time series and to estimate Annual Percent Changes (APCs) and Average Annual Percent Changes (AAPCs) over predefined timeframes. The coverages for DTP1 and MCV1 exhibit a similar trend, overall characterized by four joinpoints, one of which is in 2019. In contrast, the coverage for DTP3 does not show a significant temporal trend and lacks joinpoints, while the vaccination coverage for MCV2 shows a steadily increasing trend, with three identified joinpoints. A comparative analysis with the pre-pandemic period reveals a significant increase in the number of countries characterized by a decreasing trend during the pandemic period for all considered vaccination coverages, as indicated by the negative AAPC values. These results highlight the effect of the pandemic on childhood vaccination coverage. Compared to a mere descriptive analysis, the temporal analysis of trends using joinpoint regression provides significant opportunities to identify variations in vaccination coverages and pinpoint areas for intervention in future vaccination strategies.

SARS-CoV-2, Tdap, and influenza vaccination during pregnancy from 2019 to 2022 in Ontario, Canada: a population-based retrospective cohort study.

Hesitancy about vaccination during pregnancy posed challenges to SARS-CoV-2 vaccination efforts. We aimed to examine rates of SARS-CoV-2 vaccination among Ontario residents who gave birth in early 2022, and to compare rates of SARS-CoV-2 vaccine uptake with rates of tetanus, diphtheria, and pertussis (Tdap) and influenza vaccination during pregnancy in 2019, 2021, and 2022. We conducted a population-based retrospective cohort study to describe vaccination rates among pregnant and comparable nonpregnant populations in Ontario using linked administrative data. Provincially insured females who had a live, in-hospital birth from Jan. 1 to Mar. 31 in 2019, 2021, or 2022 were our primary cohort. Using log-binomial regression, we tested associations between SARS-CoV-2 (2022) and Tdap and influenza (2019, 2021, 2022) vaccination status, with birth group and covariates. We compared SARS-CoV-2 vaccination status with the status of a matched cohort of nonpregnant females and conducted subgroup analyses by age and prenatal clinician type. Among birthing people, 78.7% received their first SARS-CoV-2 vaccine dose and 74.2% received a second dose. The rate was significantly higher among nonpregnant comparators (dose 1: relative risk [RR] 0.94, 95% confidence interval [CI] 0.93-0.94; dose 2: RR 0.91, 95% CI 0.90-0.91). However, the rate of SARS-CoV-2 vaccination uptake among birthing people was higher than uptake of Tdap or influenza vaccination. Tetanus, diphtheria, and pertussis vaccination increased over time from 22.2% in 2019 to 32.6% in 2022, and influenza vaccination rose to 35.3% in 2021 but returned to prepandemic levels in 2022 (27.7%). Vaccination rates were lower among pregnant people who were young, multiparous, or residents of rural or economically deprived areas for all 3 vaccines. Rates of SARS-CoV-2 vaccination were lower among pregnant people than among nonpregnant comparators but were higher than rates of routinely recommended Tdap and influenza vaccinations. Pandemic urgency may have overcome a great deal of hesitancy about vaccinating against SARS-CoV-2 during pregnancy in 2022, but uptake of routinely recommended vaccines in pregnancy remains a challenge. Clinicaltrials.gov, no. NCT05663762.

Interleukin 38 reduces antigen-presentation capacity and antibody production after vaccination

The mechanisms that underpin low vaccine responses, which can lead to inadequate protection against infection, are still partially unclear. Interleukin (IL)-38 is a member of the IL-1 family, expressed by B cells among others, that regulates inflammatory responses. A recent study shows that IL-38 suppresses plasma cell generation and antibody production upon immune activation.We hypothesis that IL-38 affects antigen-presentation capacity of innate immune cells, effecting antibody production. Here, we investigated the effect of recombinant human IL-38 on human peripheral blood mononuclear cells and myeloid-derived DCs regarding cytokine production, phagocytosis, and expression of MCH II and co-stimulatory proteins in vitro, and further relate circulating plasma IL-38 concentrations to antibody responses in a cohort of 75 females aged 18–48 vaccinated with BCG and Tdap-IPV.To this end, we found that IL-38 decreased the expression of HLA-DR, HLA-DM, and CD83 on PBMCs, and CD40 and CD86 on MDDCs. IL-38 further impaired phagocytosis capacity of monocytes. Lastly, antibody production against diphtheria toxoids up to eight months post-vaccination was negatively associated with IL-38 plasma concentrations.These data suggest that IL-38 could dampen the effectiveness of antigen-presentation and phagocytosis, and could therefore modulate the immunogenicity of some vaccine types.

Increased Identification of Vaccines for Vaccine Safety Surveillance Through Linkage With the Minnesota Immunization Information Connection as of December 31, 2023.

The HealthPartners' Vaccine Safety Datalink (VSD) team maintains standardized files of vaccines from medical and pharmacy claims and electronic health records (established data sources) for safety surveillance. Since 2021, for selected vaccines, data from the Minnesota Immunization Information Connection (MIIC), Minnesota's immunization information system, have been added to the HealthPartners' VSD files. We examined how MIIC data have enhanced the identification of novel and routine vaccines. We describe the approach to incorporating MIIC data. We determined and compared the number and proportion of vaccines identified from established data sources with the additional capture of vaccine data identified from MIIC, in which age group and period of observation varied by vaccine. As of December 31, 2023, of 1 099 411 people in the HealthPartners' VSD cohort, 1 001 400 people (91%) were linked with an MIIC record. Across all data sources, for the full cohort, >2.7 million COVID-19 vaccine doses were recorded since 2020, >4000 mpox vaccine doses since 2022, >7.3 million influenza vaccine doses since 2004, >600 000 human papillomavirus (HPV) vaccine doses since 2006, and >1.1 million diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine doses since 2004. For COVID-19 vaccines, about 30% of vaccine doses were exclusively captured from MIIC, with the remaining 70% from established data sources. For the mpox vaccine, about 42% were exclusively from MIIC. For influenza, HPV, and DTaP vaccines, about 20%, 14%, and 17%, respectively, were exclusively identified from MIIC. Incorporation of data from state immunization information systems into existing vaccine data files can enhance monitoring on the safety of novel vaccines administered outside traditional health care settings and can enhance data quality for routine childhood and adult vaccines.

Vaccination Coverage by Age 24 Months Among Children Born During 2017-2021 - U.S.-Affiliated Pacific Islands.

Childhood vaccination is one of the most successful public health interventions to improve life expectancy, decrease health care costs, and reduce the spread of preventable diseases. Using data from jurisdictional immunization information systems, vaccination coverage by age 24 months among children born during 2017-2021 in the U.S.-affiliated Pacific Islands was estimated for all vaccines included in jurisdictional programs. Progress toward the U.S. Healthy People 2030 and World Health Organization Immunization Agenda 2030 vaccination goals of ≥90% coverage by age 24 months with recommended vaccines was inconsistently met across jurisdictions. For example, coverage by age 24 months with ≥1 dose of measles, mumps, and rubella vaccine ranged from 68.2% to 91.6% by birth cohort in Federated States of Micronesia and from 87.4% to 96.6% in Palau; coverage with ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) ranged from 39.6% to 60.6% in Federated States of Micronesia and from 73.4% to 85.4% in Palau. Coverage as of June 1, 2024, increased for all vaccines across all jurisdictions and birth cohorts, indicating catch-up vaccination after age 24 months. For example, coverage with ≥4 doses of DTaP by June 1, 2024, ranged from 74.0% to 84.4% in American Samoa by birth cohort and from 91.6% to 94.8% in Palau. This report is the first comprehensive analysis of trends in childhood vaccination coverage in the U.S.-affiliated Pacific Islands; data in this report can be used to determine where additional efforts are needed to assess reasons for delayed vaccination of children and strategies to mitigate vaccination delays, specific to each jurisdiction.

Effectiveness Of Local Cold Application, Manual Pressure, Shot Blocker And Standard Injection Procedure During Tetanus Diphtheria (Td) Vaccine Booster Immunization In Reducing Pain At The Intramuscular Injection Site Of Children Studying In Selected Schools: A Systematic Review

Effectiveness Of Local Cold Application, Manual Pressure, Shot Blocker And Standard Injection Procedure During Tetanus Diphtheria (Td) Vaccine Booster Immunization In Reducing Pain At The Intramuscular Injection Site Of Children Studying In Selected Schools: A Systematic Review

False-Positive Human Immunodeficiency Virus-1 Test Results With Rapid Seroreversion After Third-Trimester Tdap Booster Vaccination.

False-positive and false-negative results in human immunodeficiency virus (HIV) testing are expected at some frequency. False-positive results have been reported in association with various conditions, including pregnancy, autoimmune disease, and infection. We present an atypical case of a pregnant patient receiving false-positive HIV results for both screening and antibody confirmatory tests after a recent routine vaccination. A 34-year-old woman, G4P1021, with a negative first-trimester HIV test result received a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) booster at 35 2/7 weeks of gestation. Test results at 36 2/7 weeks of gestation were positive in both HIV-1/2 antigen-antibody screening and a confirmatory HIV-1 antibody differentiation immunoassay, but follow-up test results at 36 5/7 weeks and later were negative. Repeat testing and erythrocyte typing confirmed that this was not a result of laboratory error or specimen mishandling. HIV antiretroviral therapy was started and was later discontinued. A scheduled primary cesarean delivery performed at 39 1/7 weeks of gestation due to breech presentation was uncomplicated. False-positive results in HIV screen and confirmation testing were associated with receipt of a Tdap vaccine booster 7 days prior. This test result pattern is similar to that seen very rarely in previous cases, and the rapid seroreversion to negative suggests an acute immunologic trigger leading to a falsely reactive antibody. Clinicians should be aware of the potential for false-positive HIV test results in patients who recently received vaccination or with other immune triggers and retest at a short interval if suspected.

Use of Haemophilus influenzae Type b-Containing Vaccines Among American Indian and Alaska Native Infants: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

Invasive Haemophilus influenzae type b (Hib) disease is a serious bacterial infection that disproportionally affects American Indian and Alaska Native (AI/AN) populations. Hib vaccination with a monovalent Hib conjugate vaccine consisting of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) conjugated to outer membrane protein complex of Neisseria meningitidis serogroup B, PRP-OMP (PedvaxHIB, Merck and Co., Inc.) has historically been preferred for AI/AN infants, who are at increased risk for invasive Hib disease, because it provides substantial protection after the first dose. On June 26, 2024, CDC's Advisory Committee on Immunization Practices (ACIP) recommended that a hexavalent, combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Hib conjugate, and hepatitis B (HepB) vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company) should be included with monovalent PRP-OMP in the preferential recommendation for AI/AN infants because of the PRP-OMP Hib component. A primary Hib vaccination series consisting of either 1) monovalent PRP-OMP (2-dose series at ages 2 and 4 months) or 2) DTaP-IPV-Hib-HepB (3-dose series at ages 2, 4, and 6 months) is preferred for AI/AN infants. DTaP-IPV-Hib-HepB is only indicated for use in infants at ages 2, 4, and 6 months and should not be used for the booster doses of Hib, DTaP, or IPV vaccines. For the booster dose of Hib vaccine, no vaccine formulation is preferred for AI/AN children; any Hib vaccine (except DTaP-IPV-Hib-HepB) should be used. This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of Hib-containing vaccines among AI/AN infants and children.

Propionic acid supplementation promotes the expansion of regulatory T cells in patients with end-stage renal disease but not in renal transplant patients.

In a previous study, we showed an anti-inflammatory effect of propionic acid supplementation in dialysis patients. The present study intends to analyze the effect of propionic acid on the chronic inflammatory state and T-cell composition in kidney transplant patients compared to dialysis patients. A total of 10 dialysis patients and 16 kidney transplant patients under immunosuppressive standard triple immunosuppressive therapy received 2 × 500 mg propionic acid per day for 30 days. The cellular immune system was analyzed before and after the propionic acid supplementation and 30-90 days thereafter as a follow-up. We measured the main immune cell types and performed an in-depth characterization of T cells including regulatory T cells (Tregs), B cells, and dendritic cells. In addition, we assessed the functional activity and antigenic responsiveness by analysis of third-party antigen-specific T cells after their stimulation by recall (tetanus diphtheria vaccine) antigen. In dialysis patients, we observed an expansion of CD25highCD127- Tregs after propionic acid intake. In contrast, the same supplementation did not result in any expansion of Tregs in transplant patients under immunosuppressive therapy. We also did not observe any changes in the frequencies of the main immune cell subsets except for CD4+/CD8+ distribution with an increase of CD4+ T cells and decrease of CD8+ T cells in the transplant population. Our data suggest that dietary supplements containing propionate might have a beneficial effect decreasing systemic inflammation in dialysis patients through Treg expansion. However, this effect was not observed in transplant patients, which could be explained by counteracting effect of immunosuppressive drugs preventing Treg expansion.

Evaluation of interventions to improve timely hepatitis B birth dose vaccination among infants and maternal tetanus vaccination among pregnant women in Nigeria

Background: Nigeria has the largest number of children infected with hepatitis B virus (HBV) globally and has not yet achieved maternal and neonatal tetanus elimination. In Nigeria, maternal tetanus diphtheria (Td) vaccination is part of antenatal care and hepatitis B birth dose (HepB-BD) vaccination for newborns has been offered since 2004. We implemented interventions targeting healthcare workers (HCWs), community volunteers, and pregnant women attending antenatal care with the goal of improving timely (within 24 hours) HepB-BD vaccination among newborns and Td vaccination coverage among pregnant women. Methods: We selected 80 public health facilities in Adamawa and Enugu states, with half intervention facilities and half control. Interventions included HCW and community volunteer trainings, engagement of pregnant women, and supportive supervision at facilities. Timely HepB-BD coverage and at least two doses of Td (Td2+) coverage were assessed at baseline before project implementation (January–June 2021) and at endline, one year after implementation (January–June 2022). We held focus group discussions at intervention facilities to discuss intervention strengths, challenges, and improvement opportunities. Results: Compared to baseline, endline median vaccination coverage increased for timely HepB-BD from 2.6% to 61.8% and for Td2+ from 20.4% to 26.9% in intervention facilities (p < 0.05). In comparison, at endline in control facilities median vaccination coverage for timely HepB-BD was 7.9% (p < 0.0001) and Td2+ coverage was 22.2% (p = 0.14). Focus group discussions revealed that HCWs felt empowered to administer vaccination due to increased knowledge on hepatitis B and tetanus, pregnant women had increased knowledge that led to improved health seeking behaviors including Td vaccination, and transportation support was needed to reach those in far communities. Conclusion: Targeted interventions significantly increased timely HepB-BD and Td vaccination rates in intervention facilities. Continued support of these successful interventions could help Nigeria reach hepatitis B and maternal and neonatal tetanus elimination goals.

Interleukin-17A (IL-17A) is involved in antibody specificity to conformational epitopes

The specificity of antibodies (Ab) is essential for the precise recognition of foreign or dangerous molecules. We have shown that mice infected with non-pathogenic Lactate Dehydrogenase Elevating Virus (LDV) inoculated with human growth hormone (hGH) or Ovalbumin (OVA), exhibit modified specificity of anti-hGH or anti-OVA Ab associated with the secretion of IFN-γ, IL-13, and IL-17.Cytokines are directly or indirectly involved in the isotypes, specificity, and affinity of Ab. Accordingly, here we investigated the effect of IL-17 neutralization on Ab specificities to OVA and Diphtheria Toxoid (DTx) in a mouse model of viral infection. Thereby, we employed an anti-cytokine “auto-vaccination” with an OVA/IL-17A complex or a Monoclonal Ab (MAb) anti-IL-17A (MM17/F3).Competitive ELISA assays were used to estimate the quality of the humoral immune response and the amount of Abs to conformational versus linear antigenic determinants. Results indicated that the OVA/IL-17A complex increased Abs levels to conformational epitopes of OVA, while LDV prolonged antibodies for a longer period. Mice treated with MM17F3 MAb showed an increase in Abs to conformational epitopes of OVA. A similar effect, confirmed by a competitive Western-blot assay, was produced by LDV. Moreover, an increased level of IgM, IgG1, and IgG2a was found in infected animals. Similarly, MAb anti-IL-17A treatment increased the proportion of Ab to conformational epitopes of DTx in uninfected mice, while LDV decreased this parameter.In conclusion, our findings demonstrate a correlation between IL-17A neutralization and a change in Ab specificity to OVA or DTx, presenting a novel strategy for obtaining Abs with higher specificity.

National Vaccination Coverage Among Adolescents Aged 13-17 Years - National Immunization Survey-Teen, United States, 2023.

Based on safety and efficacy data, vaccinations are the best defense to protect persons and communities from serious vaccine-preventable diseases. The Advisory Committee on Immunization Practices recommends routine vaccination of adolescents aged 11-12 years with three vaccines including tetanus, diphtheria, and acellular pertussis vaccine; quadrivalent meningococcal conjugate vaccine; and human papillomavirus vaccine. CDC analyzed data from the 2023 National Immunization Survey-Teen for 16,658 adolescents aged 13-17 years (born during January 2005-December 2010) to assess vaccination coverage in 2023, recent trends in coverage by birth year, and trends in coverage by eligibility for the Vaccines for Children (VFC) program and birth year. In 2023, coverage with all routine vaccines recommended for adolescents was similar to coverage in 2022. Vaccination coverage among VFC-eligible adolescents was generally stable during the COVID-19 pandemic, except for a decrease in the percentage of VFC-eligible adolescents who were up to date with HPV vaccination by age 13 years among those born in 2010 compared with those born in 2007. Whereas coverage differences were found between VFC-eligible and non-VFC-eligible adolescents before the COVID-19 pandemic, coverage was similar among the most recent birth years in the survey. Providers should make strong recommendations for all routine vaccines and review adolescent vaccination records to verify if adolescents are up to date with all recommended vaccines.

Seroprevalence of anti-diphtheria toxoid antibody and implications for vaccination policy in Vietnam’s South-central coast: a cross-sectional study

BackgroundDiphtheria 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.MethodsThis 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.ResultsThe 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.ConclusionIt 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.

Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program - United States, 1994-2023.

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.