Search Results (59)

Background/Objectives: Chemically or genetically detoxified pertussis toxin (PTx) is a crucial antigen component of the acellular pertussis vaccine. Chemical detoxification using glutaraldehyde generally causes significant structural changes to the toxin. However, how these structural changes in PTx affect its antigenic properties remains unclear. Additionally, there is limited knowledge regarding how many alterations in antigenic properties impact immunogenicity. Methods: To investigate the impact of structural changes on antigenic properties, we developed a sandwich ELISA to quantify the neutralizing epitopes on PTx. Subsequently, we analyzed different PTx toxoid (PTd) preparations with the assay. Additionally, we assessed the immunogenicity of various acellular pertussis vaccine candidates containing these PTd preparations. Finally, the assay was applied to evaluate the consistency of commercial batches of PTx and PTd intermediates. Results: The assay demonstrated reasonable specificity, accuracy, and precision, and it was sensitive enough to quantify variations in neutralizing epitopes among different PTd samples that shared the same protein concentration. Importantly, we found a positive correlation between the number of neutralizing epitopes in detoxified PTx and its immunogenicity, indicating that the amount of neutralizing epitopes present determines the immunogenicity of glutaraldehyde-inactivated PTx. Moreover, commercial batches of PTx and PTd intermediates exhibited minor variations in neutralizing epitopes. Conclusions: These findings have significant implications for developing acellular pertussis vaccines as they highlight the importance of preserving the neutralizing epitopes of PTx during detoxification to ensure the vaccine’s effectiveness. This assay is also valuable for the quality control of PTd as it more accurately represents the actual antigenic changes of PTx. Full article

Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective efficacy of DTaP-Hib-MCV4 in animal models. Acute and long-term toxicity studies were conducted in Sprague-Dawley (SD) rats with equal numbers of male and female animals. Immunogenicity was assessed in female NIH mice and SD rats using a three-dose regimen at 14-day intervals. Orbital blood was collected 14 days post-immunization to measure IgG titers against pertussis, diphtheria, tetanus, Hib, and meningococcal antigens. The protective efficacy was determined using potency tests for the pertussis, diphtheria, and tetanus components; passive protection studies for Hib; and serum bactericidal antibody (SBA) titers against A/C/Y/W135 meningococcal serogroups. Results: Acute and repeated-dose toxicity studies in SD rats showed no signs of abnormal toxicity or irritation at either high (three doses/rat) or low (one dose/rat) doses levels. The no-observed-adverse-effect level (NOAEL) for DTaP-Hib-MCV4 was established at three doses/rat after 8 weeks of repeated intramuscular administration and a 4-week recovery period. Specific IgG antibodies against all the vaccine components were detected in animal sera at both one and three doses/rat, with no evidence of immunotoxicity. Following two-dose primary immunization in murine models, the combined vaccine elicited robust antigen-specific antibody responses, with geometric mean titers (GMTs) as follows: 1,280,000 for pertussis toxin (PT); 761,093 for filamentous hemagglutinin (FHA); 1,159,326 for pertactin (PRN); 1,659,955 for diphtheria toxoid (DT); 1,522,185 for tetanus toxoid (TT); 99 for Haemophilus influenzae type b (Hib); and 25,600, 33,199, 8300, and 9051 for serogroups A, C, Y, and W135 of Neisseria meningitidis, respectively. In the rat models, three-dose primary immunization also elicited robust antigen-specific antibody responses. Protection studies demonstrated efficacy against pertussis, tetanus toxin, and diphtheria toxin challenges. In the Hib challenge study, none of the 10 animals given anti-DTaP-Hib-MCV4 antiserum developed bacteremia after the live Hib challenge (vs. 5814/0.1 mL in the negative control, p < 0.001). In addition, the SBA titers against meningococcal serogroups exceeded the protective threshold (≥1:8) in 92.2% of the immunized mice and 100% of the immunized rats. Crucially, the combined vaccine induced potent immune responses and protective efficacy, with antibody levels and protection against each component antigen comparable to or greater than those of the individual components: DTaP, Hib, and MCV4. Conclusions: These findings demonstrate that the DTaP-Hib-MCV4 combined vaccine is both safe and immunogenic, supporting its potential as a viable alternative to individual vaccines. This combined vaccine may streamline immunization programs and enhance vaccination coverage. Full article

Background: Co-administration of vaccines can impact the immune response and safety. We aim to systematically review the current scientific literature and find evidence regarding the immunogenicity and safety of pneumococcal vaccines co-administered with common vaccines that are recommended for travelers, including hepatitis A, hepatitis B, yellow fever, tetanus, diphtheria, and acellular pertussis (Tdap), Japanese encephalitis, rabies, typhoid, or meningococcal (MCV) vaccine in adults (18 years or older). Methods: We followed the PRISMA 2020 guidelines and used the PICOS process to select the keywords. We searched PubMed, Web of Science, Scopus, EMBASE, and Google from 1 January 2000 to 30 June 2024. We included randomized controlled trials, non-randomized controlled trials, observational studies, case series, and case reports in adults, all published in English. Results: Out of 598 articles screened, 6 studies were included in our study. Three studies involved immunocompetent individuals, and three involved immunocompromised individuals. Co-administration of pneumococcal vaccine with Tdap or Hepatitis A in immunocompetent individuals was safe and immunogenic. Similar findings were reported for immunocompromised individuals when pneumococcal vaccines were co-administered with Tdap, hepatitis A, and hepatitis B. However, no reports investigated the co-administration of yellow fever, rabies, Japanese encephalitis, and typhoid. Two non-randomized studies in immunocompromised individuals had a high risk of bias. Conclusions: The studies collectively indicate that the co-administration of pneumococcal vaccines with Hepatitis A and Tdap vaccines in adult immunocompetent and immunocompromised individuals is safe and immunogenic. However, a knowledge gap remains, and further high-quality studies are needed, particularly due to the limited number of studies and the potential risk of bias. Full article

Maternal immunization is a key strategy for protecting pregnant individuals and newborns from infectious diseases. This review examines the mechanisms and benefits of maternal immunization, with a focus on transplacental IgG transfer and immune system interactions. We provide an overview of current recommendations and the safety and efficacy profiles of maternal vaccines, including influenza, tetanus–diphtheria–acellular pertussis (Tdap), respiratory syncytial virus (RSV), COVID-19, and hepatitis B. Additionally, we analyze the barriers to maternal immunization, such as misinformation, vaccine hesitancy, and disparities in healthcare access, while exploring potential strategies to overcome these challenges through targeted educational initiatives, improved provider communication, and policy-driven interventions aimed at increasing vaccine confidence and accessibility. Finally, this review highlights recent innovations and future directions in maternal immunization, including emerging vaccines for Group B Streptococcus and cytomegalovirus. Expanding immunization programs and advancing research on maternal–fetal immunity are essential to optimizing vaccination strategies, improving public health outcomes, and reducing the global burden of infectious diseases. Full article

Background/Objectives: The current national vaccination program does not completely control the transmission of Bordetella pertussis in Croatia. This cross-sectional seroprevalence study aimed to measure the prevalence of IgG antibodies to pertussis toxin (IgG-anti-PT) in regularly vaccinated Croatian children of 6–18 years of age and to estimate the duration of pertussis vaccine-induced immunity elicited by the National Immunization Program (NIP) with respect to the transition from a mixed acellular pertussis (DTaP) and whole-cell pertussis (DTwP) vaccine regimen to a DTaP regimen. Materials and Methods: Single-serum IgG-anti-PT concentrations were measured using a commercial enzyme-linked immunosorbent assay (ELISA) and analyzed in twelve age groups from 2020 to 2023. According to the manufacturer’s classification, IgG-anti-PT concentrations of <40 IU/mL, 40–100 IU/mL, and >100 IU/mL were considered negative, borderline, and positive, respectively. Results: In total, 1314 sera samples were collected and analyzed. Most subjects had an IgG-anti-PT concentration < 40 IU/mL (95.1%). This study sample’s IgG-anti-PT geometric mean concentration (GMC) was very low. Despite different vaccination backgrounds, the waning of IgG-anti-PT concentration was observed in Croatian children and adolescents. Discussion: In the present study, 0.53% of subjects were seropositive (>100 IU/mL). Regardless of the low quantity of IgG-anti-PT, we estimated that a degree of protection against pertussis persisted for at least 8–9 years based on a small increase in IgG-anti-PT GMC in 15–18-year-olds, indicative of an ongoing B. pertussis circulation in Croatia. Although introducing a booster pertussis vaccine could be suitable for young adolescents to strengthen their immunity, before such a recommendation, it would be useful to initiate further research to complement the results obtained in this study. Full article

Background/Objectives: Hematopoietic stem cell transplantation (HSCT) can potentially cure hematological malignancies; however, post-transplant patients have a high risk of infection owing to their immunocompromised status. Vaccination against pathogens, such as diphtheria, tetanus, pertussis, and polio, is essential post-transplantation, but neither the long-term efficacy of vaccines nor the optimal vaccination schedule has been fully established. Methods: In this prospective observational study, we assessed the short- and long-term immunogenicity of three doses of the diphtheria, tetanus, acellular pertussis, and inactivated poliovirus (DTaP-IPV) vaccines or DTaP vaccines in 29 adult allogeneic HSCT (allo-HSCT) recipients, with antibody levels measured at baseline, 1–3 months post-vaccination, and 1-year after vaccine completion. Results: At baseline, a substantial proportion of patients lacked protective antibody levels for the targeted pathogens. However, within 1–3 months post-vaccination, seropositivity rates significantly increased, reaching 78–100% for diphtheria, tetanus, pertussis, and poliovirus. Despite this, antibody levels significantly declined 1-year post-vaccination, especially for pertussis, with only 58–65% of patients maintaining protective levels. In contrast, 85–96% of patients retained protective levels for diphtheria, tetanus, and poliovirus, although antibody values also decreased. Compared to human leukocyte antigen (HLA)-mismatched cases, HLA-matched cases showed significantly higher antibody levels for diphtheria, pertussis, and poliovirus types 1 and 3. Conclusions: This study demonstrates the short-term effectiveness of DTaP-IPV and DTaP vaccines in adult allo-HSCT patients but emphasizes the challenge of maintaining long-term immunity. Given the difficulties in sustaining long-term vaccine efficacy in allo-HSCT recipients, particularly in HLA-mismatched cases, re-evaluating the current vaccination schedule may be necessary to maintain protection. Full article

Background/Objectives: The Italian National Plan for Vaccine Prevention 2017–2019 recommended tetanus, diphtheria, and acellular pertussis vaccines (Tdap) for pregnant women, irrespectively of their immunization history. This study aims to describe the coverage rate trends for Tdap vaccination in pregnancy and evaluate the differences by socioeconomic status. Methods: This is a retrospective analysis within a health equity audit of the Local Health Authority of Reggio Emilia on vaccination in pregnancy from 2018 (a local vaccination campaign) to 2023. All women residents in our area who gave birth during that period were included and linked to the electronic Registry of Immunization Service. The vaccination coverage in pregnant women was analyzed over time and stratified by pregnant women’s sociodemographic and obstetric characteristics. Results: The coverage of Tdap in pregnant women of the Province of Reggio Emilia increased from 15.9% in 2018 to 53.9% in 2023. The coverage was higher among Italians, women with higher educational levels (aPR 1.49 (CI95%1.41–1.57)), within 31–35 years of age (aPR 1.37 (CI95% 1.28–1.46)), occupied, nulliparous (aPR multiparous vs nulliparous: 0.76 (0.74; 0.78)), and followed in the private sector (aPR 1.07 (1.03–1.11)). Inequalities in coverage increased during the study period for women assisted in the private sector, while decreased or remained stable for women assisted in the context of public services. Conclusions: The vaccination promotion campaign in Reggio Emilia helped increase Tdap coverage in pregnancy from 16 to 53%. Nevertheless, the coverage rates of the most disadvantaged women are still several points lower than the average. Full article

Background/Objectives: An assay for protein content is essential but insufficient for quality control of acellular pertussis vaccines, which might consist of up to five components, each needing individual quantification. Generally, purified pertussis antigens such as pertussis toxin (PTx), filamentous haemagglutinin (FHA), and pertactin (PRN) should be detoxified or stabilized chemically before being formulated into vaccine bulk. The use of chemical agents like formaldehyde and glutaraldehyde can alter the immunological reactivity of these antigens, rendering direct assays by methods such as ELISA ineffective. Methods: In this study, a simple method based on single radial diffusion (SRD) using low concentrations of polyclonal antisera against PT toxoid (PTd), FHA, and PRN was developed. By adding a detergent, diffusible subunits are produced regardless of the original physical state of the antigens, making it suitable for quantifying these antigens after chemical treatment. Results: The assay has shown good specificity, accuracy, and precision. Furthermore, it can differentiate between preparations with the same protein concentration but different antigenic contents. A significant positive correlation between the antigen content and the in vivo immunogenicity has also been demonstrated. Conclusions: An assay for quality control and consistency monitoring of combined vaccines containing acellular pertussis antigen components has been established. Full article

Background: The genetic background of Toll-like receptor 4 (TLR4) proved to be important in the induction of immune protection against Bordetella pertussis infection in humans. Currently, the evaluation of the acellular pertussis (aP) vaccine depends largely on using different mouse strains, while the TLR4 genotype of different mouse strains in response to pertussis toxin (PT) is not carefully determined. The current study was designed to determine the differences in TLR4 genotype and TLR4 pathway-related cytokines in response to PT stimulation among mouse strains of ICR, NIH, and BALB/c. Method: We first determined the single-nucleotide polymorphisms (SNPs) in the TLR4 gene by using first-generation sequencing. Then, the cellular response, including the TLR4 mRNA expression and TLR4 signaling-related cytokines, of immune cells from different mouse strains after PT stimulation was determined. Result: Three missense mutation sites (rs13489092, rs13489093, rs13489097) of the TLR4 gene were found. ICR mice were homozygous without mutation, NIH mice were partially heterozygous, and BALB/c mice were homozygous with a missense mutation. The expression of TLR4 was repressed while the downstream cytokines were upregulated after PT stimulation differently among mouse strains. The IFN-β cytokine of the TRIF pathway was significantly increased in ICR mice (p < 0.05). The IL-6 cytokine of the MyD88-dependent pathway was significantly increased in BALB/c mice (p < 0.05). The identified SNPs of the TLR4 gene in different mouse strains might account for the differences in cytokines levels determined after PT stimulation. Conclusions: Our studies might provide useful referees to reduce the mouse-derived difference in the determination of vaccine titer and increase the comparability of the vaccine from different origins, as different mouse strains were used for vaccine development in different countries. Full article

School vaccination programs are crucial for achieving high immunisation coverage among adolescents, but substantial disparities exist across schools and regions. This ecological study aimed to determine associations between school characteristics and vaccination coverage for diphtheria–tetanus–acellular pertussis (dTpa) and human papillomavirus (HPV) vaccines among year 7 students in southeastern Sydney. An analysis of data from 70 mainstream schools participating in the 2019 South Eastern Sydney Local Health District School Vaccination Program utilised quasi-Poisson regression models to assess associations between vaccination coverage and school attendance, socio-educational status, Aboriginal enrolments, language background other than English (LBOTE), school sector (government, Catholic, or independent), and coeducation status. Median school coverage was 88% for dTpa, 88% for HPV—girls, and 86% for HPV—boys, with interquartile ranges of 82–93%, 84–92%, and 78–91%, respectively. Higher school attendance was associated with increased dTpa vaccination coverage (PR 1.14, 95% CI 1.02–1.27). Single-sex schools showed higher HPV vaccination coverage compared to coeducational schools for both girls (PR 2.24, 95% CI 2.04–2.46) and boys (PR 1.89, 95% CI 1.72–2.08). No significant associations were found for ICSEA, Aboriginal enrolments, LBOTE, or school sector. School attendance and coeducational status significantly influenced vaccination coverage, with differential impacts on dTpa and HPV vaccines. These findings highlight the need for targeted strategies to address disparities in school-based vaccination programs. Research using qualitative methods could be useful to understand the beliefs and attitudes contributing to these disparities in vaccine uptake so that programs can be tailored to maximise participation. Full article

Background: Pertussis, or whooping cough, is a global public health concern. Pertussis vaccines have demonstrated good protection against Bordetella pertussis infections, but their effectiveness against Bordetella parapertussis remains debated due to conflicting study outcomes. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of pertussis vaccines in protecting children against B. parapertussis infection. A comprehensive search of PubMed, Web of Science, and Scopus databases was conducted, and randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. Results: The meta-analysis, involving 46,533 participants, revealed no significant protective effect of pertussis vaccination against B. parapertussis infection (risk ratio: 1.10, 95% confidence interval: 0.83 to 1.44). Subgroup analyses by vaccine type and study design revealed no significant protection. The dearth of recent data and a limited pool of eligible studies, particularly RCTs, underscore a critical gap that warrants future research in the domain. Conclusions: These findings offer crucial insights into the lack of effectiveness of pertussis vaccines against B. parapertussis. Given the rising incidence of cases and outbreaks, coupled with the lack of cross-protection by the existing vaccines, there is an urgent need to develop vaccines that include specific antigens to protect against B. parapertussis. Full article

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+ T_RM 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+ T_RM 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+ T_RM 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. Full article

The Haemophilus influenzae type B (Hib) conjugate vaccine is the most effective way to prevent Hib infection in infants and young children, and it is designed to induce the production of antibodies against polyribosylribitol phosphate (PRP) to protect babies from infection. However, the mechanism of immunity induced by the Hib vaccine is not fully understood. Recently, with the development of the combination diphtheria and tetanus toxoids and acellular pertussis vaccines (DTaP), increasing numbers of manufacturers have begun to develop DTaP-based combination vaccines, like the combination vaccine diphtheria and tetanus toxoids and acellular pertussis and Hib conjugate vaccine (DTaP-Hib), which contains adjuvants. However, the Hib vaccine does not contain adjuvants. It was theorized that the Hib antigen has poor compatibility with aluminum adjuvants for unclear reasons. Therefore, understanding the mechanism of the Hib-vaccine-induced immune response and the influence of adjuvants on the Hib vaccine is of great significance. In this paper, we immunized BalBc mice with either the Hib vaccine or the Hib vaccine that adsorbs aluminum adjuvants (Hib-Al). Here, we analyzed the anti-PRP antibody level and immune response of different cells using cell and cytokine levels. We found that the Hib vaccine could induce a humoral and cellular immune response, and the Hib-Al vaccine could induce greater quantities of IFN-γ, IL-4, and IL-6 and more antigen-specific antibodies through B cells, Th1, Th2, and ILC3s in the spleen. Together, our findings demonstrate the serologic responses and immune response in terms of cell and cytokine levels induced by the Hib vaccine, and they also imply that the addition of aluminum hydroxide adjuvant could enhance the function of the Hib vaccine, which preliminarily reveals the mechanism of immune response induced by the Hib-related vaccine. Full article

Introduction: Patients with inflammatory bowel disease (IBD) on biologic therapies are at increased risk of infections, emphasizing the importance of immunization. This study aimed to assess vaccination prevalence among patients with IBD on specific biologic therapies. Methods: A survey-based cross-sectional study was conducted at an IBD center, including patients receiving different biologic therapies from 1 January 2022 to the 30 April 2023. Demographic and vaccination data were collected using patient electronic records and patient interviews. Results: A total 394 patients (100%) received the measles, mumps, rubella (MMR), tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine. A total of 79 patients (20%) received the influenza vaccine, 40 patients (10.2%) were vaccinated against hepatitis A (HAV), and 34 patients (8.6%) received the pneumococcal vaccine. From the 103 female patients who are eligible to take human papillomavirus (HPV) vaccine, only 7 (6.8%) received it. Out of the 100 eligible patients above the age of 50, only 9 (9%) received the herpes zoster (HZ) vaccine. Conclusion: The uptake of certain vaccines such as Hepatitis B (HBV), seasonal influenza, HAV, pneumococcal, HZ and HPV vaccines among patients with IBD were below expectations. These findings highlight the need for interventions to improve patients’ awareness and adherence to prevent infectious complications in patients with IBD. Full article

Italian occupational physicians (OPs) are instrumental in promoting vaccination practice in occupational settings, and this study aims to characterize their attitudes, knowledge, and practices (collectively, KAP) towards immunization practice in women of childbearing age. A convenience sample of 120 OPs (50.8% males, mean age of 48.2 ± 5.9 years old) completed a structured online questionnaire (potential recipients: 2034; response rate: 5.9%) assessing their understanding of official recommendations, their general knowledge of vaccine practice, their attitudes towards vaccines, and their risk perception about vaccine-preventable infectious diseases. The sampled OPs exhibited a good understanding of official recommendations, and they were largely favorable towards vaccination of pregnant women. Knowledge status was relatively good (potential range 0 to 100%, average score 22 74.5% ± 18.2), while risk perception towards sampled disorders was heterogenous: the greatest was the one for SARS-CoV-2 (52.7% ± 32.9), followed by seasonal influenza (45.3% ± 31.6), and pertussis (37.8% 24 ± 28.2). The main predictors for promoting vaccination were higher knowledge about seasonal influenza vaccine (SIV; adjusted Odds Ratio [aOR] 102.2, 95% Confidence Interval [95%CI] 9.68–1080.26), tetanus-diphtheria-acellular pertussis vaccine (Tdap; aOR 12.34, 95%CI 2.62; 58.22) 27 and SARS-CoV-2 vaccine (aOR 14.76, 95%CI 2.74–79.69). A better attitude towards SIV was positively associated with previous vaccination of the respondent (aOR 4.90, 95%CI 1.19–20.14), while higher risk perception towards SIV was characterized as a negative predictor (aOR 0.04, 95%CI 0.01–0.35), as was working as an OP in healthcare facilities (aOR 0.03, 95%CI 0.01–0.43). Tdap was positively associated with male gender of respondents (aOR 10.22, 95%CI 2.60 to 40.24) and higher risk perception about pertussis (aOR 10.38, 95%CI 1.47 to 73.47). Overall, our data suggest that improving the understanding of OPs about the health burden of frequently encountered pathogens could be instrumental in increasing their involvement in the promotion of vaccine practice. Because of the low rate of response to our survey, our conclusions remain tentative. Full article