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Keywords = acellular pertussis vaccines

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13 pages, 527 KB  
Article
Factors Associated with Antibiotic Initiation After DaBT-Hib-IPV Vaccination in NICU-Hospitalized Preterm Infants: The Role of C-Reactive Protein
by Hüseyin Şimşek, Mustafa Akçalı, Mehtap Durukan Tosun, Berfin Özmen and Suna Özdem
J. Clin. Med. 2026, 15(15), 5934; https://doi.org/10.3390/jcm15155934 - 29 Jul 2026
Viewed by 320
Abstract
Objective: The purpose of this study was to evaluate the factors, particularly post-vaccination C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR), associated with the clinical decision to initiate antibiotic treatment following the 2-month diphtheria–acellular pertussis–tetanus–Haemophilus influenzae Type B–inactivated poliovirus (DaBT-Hib-IPV) vaccine in [...] Read more.
Objective: The purpose of this study was to evaluate the factors, particularly post-vaccination C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR), associated with the clinical decision to initiate antibiotic treatment following the 2-month diphtheria–acellular pertussis–tetanus–Haemophilus influenzae Type B–inactivated poliovirus (DaBT-Hib-IPV) vaccine in hospitalized infants. Methods: A retrospective review was conducted on the medical records of 46 infants. The study included infants hospitalized between 2022 and 2024 at Mersin City Training and Research Hospital who received the 2-month vaccine and subsequently underwent post-vaccination laboratory testing. Infants were categorized based on whether they received antibiotic treatment. Results: Antibiotics were administered to 20 infants, and 26 were observed without any treatment. Despite having a significantly higher gestational age (p = 0.027), the hospital stays of the antibiotic group were significantly longer (median 99 vs. 78 days, p < 0.001). C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) were elevated in the antibiotic group (CRP = 2.82 vs. 1.63 mg/dL, p < 0.001; NLR= 0.90 vs. 0.72, p = 0.041). Culture positivity was low in antibiotic recipients (3/20, 15%). CRP was the only independent predictor of antibiotic administration when adjusted for gestational age and weight at vaccination (Exp(B) = 3.997, p = 0.003). Conclusions: In this cohort of NICU-hospitalized, predominantly preterm infants, a population that does not represent the general population of vaccinated 2-month-old infants, post-vaccination elevations in CRP and NLRs were associated with the clinical decision to initiate antibiotic treatment; however, in the absence of a validated infection reference standard, these markers cannot be assumed to reliably differentiate true infection from vaccine-induced inflammation. To prevent unnecessary antibiotic use and optimize patient management, these markers must be evaluated in conjunction with clinical findings, culture results, and supplementary biomarkers. Full article
(This article belongs to the Section Clinical Pediatrics)
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21 pages, 2611 KB  
Article
Development of High-Throughput Serum Bactericidal Assays for Bordetella pertussis to Evaluate BPZE1
by Peter Goldstein, Tania Gensale, Shannon Harris, Tina M. Green, Stephanie Noviello, Keith Rubin, Camille Locht, Breeze Cavell, Andrew Gorringe and Luc Gagnon
Vaccines 2026, 14(6), 492; https://doi.org/10.3390/vaccines14060492 - 30 May 2026
Viewed by 530
Abstract
Background/Objectives: Pertussis, caused by Bordetella pertussis, remains a global health problem, despite high vaccine coverage. In countries with high acellular pertussis vaccine (aPV) coverage, pertactin-negative B. pertussis strains emerged due to vaccine pressure on the sole bactericidal target of aPVs. In contrast, [...] Read more.
Background/Objectives: Pertussis, caused by Bordetella pertussis, remains a global health problem, despite high vaccine coverage. In countries with high acellular pertussis vaccine (aPV) coverage, pertactin-negative B. pertussis strains emerged due to vaccine pressure on the sole bactericidal target of aPVs. In contrast, the live attenuated intranasal vaccine BPZE1 induces bactericidal antibodies to multiple antigenic targets that kill pertactin-positive and pertactin-negative B. pertussis strains. Here, we developed two high-throughput human complement-mediated serum bactericidal assays (SBA) using clinical samples to demonstrate bactericidal activity against B. pertussis. Methods: Assay accuracy, precision, linearity, range and robustness of the SBAs against pertactin-positive and pertactin-negative B. pertussis strain B1917 were determined using a panel of commercial and clinical trial samples. The assay was used to analyze a cohort of BPZE1 and tetanus–diphtheria–acellular pertussis (Tdap) vaccinee samples at baseline and 28 days post-vaccination from a phase 2b clinical trial. Results: Inter- and intra-assay variability of both assays had coefficients of variation for repeatability < 20% and for intermediate precision of <30%. The assays measured titers ranging from ~8 to ~20,000 and showed high linearity (R2 > 0.98) between bactericidal titers and serum dilutions. On clinical samples, BPZE1 induced similar bactericidal activity as Tdap against pertactin-positive B. pertussis, despite inducing lower anti-aP antigen IgG concentrations than Tdap. Additionally, BPZE1 induced serum bactericidal activity against pertactin-negative B. pertussis, while Tdap did not. Conclusions: High-throughput SBAs were developed and qualified against pertactin-positive and pertactin-negative B. pertussis, enabling measurement of 120 samples per day per analyst. These assays will support clinical development of next-generation pertussis vaccines, including BPZE1. Full article
(This article belongs to the Special Issue Vaccine Advancement, Efficacy and Safety: Feature Papers)
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11 pages, 201 KB  
Article
Improving Routine Childhood Vaccination Coverage Through Registry-Driven Telephone Outreach: A Large Pre–Post Study from the Federation of Bosnia and Herzegovina
by Stela Stojisavljevic, Mirza Palo and Faris Dizdar
Vaccines 2026, 14(6), 483; https://doi.org/10.3390/vaccines14060483 - 29 May 2026
Viewed by 1074
Abstract
Background: Vaccination coverage declined in many countries during the COVID-19 pandemic, including in Bosnia and Herzegovina. We evaluated a telephone-based outreach intervention implemented in primary healthcare facilities (PHCs) in the Federation of Bosnia and Herzegovina. The intervention targeted missed routine vaccinations among children [...] Read more.
Background: Vaccination coverage declined in many countries during the COVID-19 pandemic, including in Bosnia and Herzegovina. We evaluated a telephone-based outreach intervention implemented in primary healthcare facilities (PHCs) in the Federation of Bosnia and Herzegovina. The intervention targeted missed routine vaccinations among children aged 0–7 years. Method: Using a programmatic, non-randomized pre–post design, healthcare teams reviewed registries to identify under-vaccinated children, and parents were contacted by phone to facilitate catch-up visits. Results: Among age-eligible children, vaccination coverage increased from 66.5% to 74.2% for measles–mumps–rubella (MMR) dose 1, from 43.4% to 51.7% for MMR dose 2, and from 50.4% to 55.9% for the fourth dose of diphtheria–tetanus–acellular pertussis-inactivated poliovirus–Haemophilus influenzae type b vaccine (DTaP-IPV-Hib). Mixed-effects models adjusting for age, sex, and clustering by facility and canton showed higher odds of vaccination post-intervention for MMR dose 1 (adjusted odds ratio [aOR] 1.65), MMR dose 2 (aOR 1.61), and DTaP-IPV-Hib dose 4 (aOR 1.39; all p < 0.001). Conclusions: These results show that registry-based, proactive outreach can yield significant improvements in routine childhood vaccination coverage in real-world settings and may be a scalable approach for decentralized health systems recovering from pandemic disruptions. Full article
25 pages, 622 KB  
Review
Bordetella pertussis Infection: From Immune Pathogenesis to Next-Generation Vaccines
by Vasiliki E. Georgakopoulou and Vassiliki C. Pitiriga
Vaccines 2026, 14(5), 384; https://doi.org/10.3390/vaccines14050384 - 24 Apr 2026
Viewed by 1255
Abstract
Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis [...] Read more.
Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article
(This article belongs to the Section Pathogens-Host Immune Boundaries)
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24 pages, 2332 KB  
Review
Revisiting Whooping Cough: Global Drivers and Implications of Pertussis Resurgence in the Acellular Vaccine Era
by Siheng Zhang, Yan Xu and Ying Xiao
Vaccines 2026, 14(1), 35; https://doi.org/10.3390/vaccines14010035 - 28 Dec 2025
Viewed by 3059
Abstract
Background: Whooping cough caused by Bordetella pertussis is re-emerging despite high vaccination coverage, with rising incidence in adolescents and adults in the acellular vaccine (aP) era. This narrative review synthesizes evidence on the drivers of this paradox and their implications for pertussis [...] Read more.
Background: Whooping cough caused by Bordetella pertussis is re-emerging despite high vaccination coverage, with rising incidence in adolescents and adults in the acellular vaccine (aP) era. This narrative review synthesizes evidence on the drivers of this paradox and their implications for pertussis control. Methods: We conducted a structured (but not fully systematic) literature search and narrative synthesis of PubMed, Web of Science, and Embase for publications from January 2000 to February 2025 using terms related to “Bordetella pertussis,” “pertussis resurgence,” “acellular vaccine,” “waning immunity,” “ptxP3,” “pertactin-deficient,” “macrolide resistance,” and “whole-genome sequencing.” English-language, peer-reviewed studies, surveillance reports, genomic analyses, and immunological investigations were included. About 1900 records met broad eligibility criteria and were screened, and key studies were selected for narrative synthesis. Results: The resurgence appears to result from three convergent factors: (1) waning and non-sterilizing aP-induced immunity, which allows bacterial colonization and transmission; (2) vaccine-driven genomic evolution of B. pertussis, marked by global dominance of the ptxP3 lineage and widespread pertactin-deficient (PRN−) strains; and (3) emergence of macrolide-resistant clones, exemplified by the MT28-Shanghai strain. Whole-genome sequencing (WGS) has been central for defining these processes and clonal sweeps under combined vaccine and antibiotic pressure, supporting a three-driver framework of waning aP immunity, vaccine-driven evolution, and macrolide resistance. Conclusions: Pertussis resurgence illustrates pathogen adaptation to human interventions. Effective mitigation requires WGS-integrated global surveillance, re-evaluation of vaccine formulations to keep pace with antigenic change, and strengthened antibiotic stewardship, alongside development of next-generation vaccines that induce durable mucosal immunity and block transmission. Full article
(This article belongs to the Section Vaccines and Public Health)
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30 pages, 6719 KB  
Article
Vaccinations for Expecting Mothers to Improve Pregnancy Care in Middle Tennessee
by Alphonso Harvey, Mohammad Tabatabai, Derek Wilus, Sofia Thomas, James E. K. Hildreth and Donald J. Alcendor
Pathogens 2025, 14(12), 1255; https://doi.org/10.3390/pathogens14121255 - 8 Dec 2025
Viewed by 1327
Abstract
Background: During pregnancy, mothers and their infants are at increased risk for complications due to COVID-19 infection, influenza, and pertussis. At the time of writing, the previous advisory committee on immunization practices (ACIP) recommended that pregnant women receive the COVID-19 vaccine, influenza, tetanus-toxoid, [...] Read more.
Background: During pregnancy, mothers and their infants are at increased risk for complications due to COVID-19 infection, influenza, and pertussis. At the time of writing, the previous advisory committee on immunization practices (ACIP) recommended that pregnant women receive the COVID-19 vaccine, influenza, tetanus-toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, as well as respiratory syncytial virus vaccinations during pregnancy. The COVID-19 pandemic greatly impacted routine vaccinations especially among medically underserved women in the South. The barriers to recommended vaccinations during pregnancy for medically underserved women in the South are unclear and require further investigation. The purpose of this study is to examine the attitudes, opinions, and beliefs of a multiracial pregnant cohort from diverse backgrounds in Central Tennessee about their experiences with the vaccines that are recommended during pregnancy. The vaccines included in the study are COVID-19, flu, and Tdap because RSV was not yet FDA-approved for pregnant women at the launch of this study. Methods: In this study, we focus on medically underserved women in Nashville, Tennessee, and the surrounding rural counties regarding vaccine acceptance and initiation of the COVID-19, influenza, and the Tdap vaccines. This study involved 208 pregnant people (100%) aged 18–49 years. All respondents were pregnant at the time of the study. The study consisted of a 26 question Redcap survey about participants’ beliefs, attitudes, opinions, and experiences with the COVID-19, flu, and Tdap vaccines during their pregnancy. Results: The randomly selected participants in the cohort were 40.4% White, 31.7% Black, 21.6% Hispanic, and 6.3% other race/ethnicity. The mothers in the cohort were young, with an average age of 27 years, most were married, and 52.8% had an annual household income before taxes of less than USD 35,000. Only 19.2% of the mothers in this study were very confident of the safety of the COVID-19 vaccine, compared to 32.7% for both the flu and Tdap vaccines. Overall, primary care providers were identified as the most trusted messengers for both disease and vaccine information for COVID-19, flu, and Tdap. However, only 11 participants out of 208 received all three of the ACIP recommended vaccines during their pregnancies in the study, barring the time-dependent vaccination for Tdap. The most common reasons for not receiving these vaccines involved concerns for the safety of themselves and their babies and a fear of needles. Conclusions: Education and awareness of ACIP-recommended vaccines during pregnancy needs improvement, and the support of primary care providers as the main driver of pregnancy vaccine initiation is essential. Full article
(This article belongs to the Special Issue Advanced Research in Influenza Vaccines and Therapies)
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12 pages, 1030 KB  
Article
Safety Evaluation of Tetanus, Diphtheria, and Acellular Pertussis Vaccine (Tdap) During Pregnancy Among Vietnamese Women
by Hien Minh Nguyen, Nhat Thang Tran, Quoc Huy Pham and Huu Nghia Cao
Vaccines 2025, 13(10), 1036; https://doi.org/10.3390/vaccines13101036 - 8 Oct 2025
Cited by 1 | Viewed by 3835
Abstract
Background: In Vietnam, the Ministry of Health recently approved the use of Tdap vaccines—Boostrix (2022) and Adacel (2024)—for administration during pregnancy, aiming to provide passive antibody transfer to protect newborns against pertussis and tetanus from birth. However, uptake remains low, largely because Tdap [...] Read more.
Background: In Vietnam, the Ministry of Health recently approved the use of Tdap vaccines—Boostrix (2022) and Adacel (2024)—for administration during pregnancy, aiming to provide passive antibody transfer to protect newborns against pertussis and tetanus from birth. However, uptake remains low, largely because Tdap is not included in the National Expanded Program on Immunization, vaccine hesitancy persists among obstetricians, and local safety data in pregnancy are limited. Methods: We conducted a prospective cohort study from September 2023 to September 2024 involving 485 pregnant women between 27 and 36 weeks of gestation at two major hospitals in Ho Chi Minh City: University Medical Center and Gia Dinh People’s Hospital. Participants received either Tdap or monovalent tetanus toxoid vaccine (TT) as a comparator. Results: Among women in the Tdap group, 49.8% reported at least one adverse event following immunization (AEFI). Local reactions were the most frequent, primarily injection-site pain (43.8%). Fatigue (12.8%) was the most common systemic reaction, followed by headache (3.9%). Grade 3 AEFIs occurred in 5% of the Tdap group and included extensive local reactions (erythema or swelling > 3 cm), high-grade fever (≥40 °C), and severe fatigue interfering with daily activities or requiring hospitalization. Women receiving Tdap had 1.52-fold higher injection-site pain compared with those receiving TT (95% CI: 0.060–0.782). Importantly, co-administration of Tdap with inactivated quadrivalent influenza vaccine (IIV4) did not increase the risk of AEFIs. Furthermore, no evidence was found that Tdap vaccination adversely affected the course of pre-existing maternal comorbidities, which remained stable throughout pregnancy. Conclusions: This first large-scale Vietnamese cohort provides reassuring evidence on the safety of Tdap vaccination during pregnancy. These findings support broader implementation of maternal Tdap immunization, including concomitant administration with IIV4, to protect both mothers and infants. Full article
(This article belongs to the Special Issue Vaccines for the Vulnerable Population)
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31 pages, 1855 KB  
Review
Pertussis—A Re-Emerging Threat Despite Immunization: An Analysis of Vaccine Effectiveness and Antibiotic Resistance
by Anna Duda-Madej, Jakub Łabaz, Ewa Topola, Hanna Bazan and Szymon Viscardi
Int. J. Mol. Sci. 2025, 26(19), 9607; https://doi.org/10.3390/ijms26199607 - 1 Oct 2025
Cited by 9 | Viewed by 5898
Abstract
Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a [...] Read more.
Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a particular problem for the pediatric population among whom the highest mortality from the disease is recorded. Several reasons for this phenomenon can be mentioned, but what is particularly important from the microbiological point of view is the correlation of the increased number of pertussis cases with the introduction of a new form of vaccine—the acellular vaccine in place of the whole-cell vaccine. In this review, we summarized the current state of knowledge on potential factors that may contribute to the decline in immunization efficacy against the pathogen. The post-vaccination response profile, symptomatic of vaccination with vaccination-acellular, is characterized by recruitment of Th2 and Th17 lymphocytes; it has been reported that in the long term, this results in insufficient activation of B cells and low titers of antibodies to key bacterial antigens (hemagglutinin, pertactin). Moreover, the immune response proceeds by bypassing the recruitment of tissue-resident memory T cells, resulting in a lack of protection against colonization of the nasal cavity by the bacterium despite vaccination. The decline in vaccination efficacy should also be attributed to the phenotypic variability of Bordetella. The popularization of the PtxP3 strain, characterized by its ability to incompletely activate immune mechanisms, poses a real threat to public health. The growing resistance of B. pertussis to standardly used antibiotics including macrolides also remains a problem. This makes it difficult to eradicate pathogens from the nasal cavity area and increases the pool of bacterial carriers in the population area. The increasing prevalence of the disease prompts reflection on more effective methods of prevention. Particularly promising in this field seem to be new vaccines, especially mucosally implemented, e.g., intranasal, or developed on the basis of B. pertussis antigens other than those used so far. Full article
(This article belongs to the Section Molecular Immunology)
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12 pages, 2630 KB  
Article
Evaluating the Relationship Between the Introduction of the Acellular Pertussis Vaccine and Whooping Cough Resurgence in the United States
by Jeegan Parikh, Ismael Hoare and Ricardo Izurieta
Vaccines 2025, 13(8), 841; https://doi.org/10.3390/vaccines13080841 - 7 Aug 2025
Cited by 7 | Viewed by 6195
Abstract
Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United [...] Read more.
Background/Objectives: The whole cell pertussis vaccine was introduced in the United States in the 1940s and switched to the acellular pertussis vaccine partially in 1992 and completely in 1997. This study examines the relationship between the resurgence of pertussis in the United States and the change in the type of pertussis vaccines. Methods: Pertussis cases from 1922 to 2024 were obtained from the CDC’s national notifiable disease surveillance system, and vaccination coverage was obtained from the WHO. A trend analysis and Pearson’s correlation test were conducted between the incidence of cases and the coverage of the third and fourth doses of the pertussis vaccine. An ANOVA test and multivariable linear regression were performed to assess the association between the type of vaccine and the number of pertussis cases. Results: The number of cases increased from 4083 in 1992 to 35,435 in 2024, with cyclical outbreaks in 2010, 2012–2014, and 2024. The third and fourth doses of pertussis vaccine coverage had mild and moderate correlations with the number of pertussis cases. The vaccine type had a significant association with the number of pertussis cases and stayed significant after adjusting for vaccination coverage. Conclusions: The switch in pertussis vaccine has impacted the epidemiology of pertussis outbreaks in the United States. A combination of factors, such as different types of immune response to vaccines, waning of immunity, and selection of non-vaccine bacterial strains, may explain the observed results. Further research on newer, improved vaccinations or alternative schedules in children needs to be conducted to address the resurgence of pertussis in this study. Full article
(This article belongs to the Special Issue Vaccination, Public Health and Epidemiology)
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12 pages, 1172 KB  
Article
The Immunogenicity of Glutaraldehyde Inactivated PTx Is Determined by the Quantity of Neutralizing Epitopes
by Xi Wang, Xinyue Cui, Chongyang Wu, Ke Tao, Shuyuan Pan and Wenming Wei
Vaccines 2025, 13(8), 817; https://doi.org/10.3390/vaccines13080817 - 31 Jul 2025
Cited by 1 | Viewed by 1444
Abstract
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. [...] Read more.
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
(This article belongs to the Special Issue New Technology for Vaccines and Vaccine-Preventable Diseases)
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20 pages, 2293 KB  
Article
An Evaluation of the Safety, Immunogenicity, and Protective Efficacy of a Combined Diphtheria–Tetanus–Acellular Pertussis, Haemophilus influenzae Type b, and ACYW135 Meningococcal Conjugate Vaccine in Murine and Rat Models
by Xiuwen Sui, Zhujun Shao, Yuanyuan Ji, Hairui Wang, Qingfu Xu, Bochao Wei, Zhuojun Duan, Chang Wang, Ying Yang, Jiayu Zhao and Tao Zhu
Vaccines 2025, 13(7), 724; https://doi.org/10.3390/vaccines13070724 - 3 Jul 2025
Cited by 3 | Viewed by 2869
Abstract
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 [...] Read more.
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
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15 pages, 2870 KB  
Systematic Review
Immunogenicity and Safety of Pneumococcal Vaccines Co-Administered with Common Travel Vaccines in Adults: A Systematic Review
by Raziyeh Niyati, Omid Rezahosseini, Christina Ekenberg, Carsten Schade Larsen and Zitta Barrella Harboe
Vaccines 2025, 13(6), 643; https://doi.org/10.3390/vaccines13060643 - 14 Jun 2025
Cited by 3 | Viewed by 2861
Abstract
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, [...] Read more.
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
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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19 pages, 689 KB  
Review
Maternal Immunization: Current Evidence, Progress, and Challenges
by Veronica Santilli, Mayla Sgrulletti, Giorgio Costagliola, Alessandra Beni, Maria Felicia Mastrototaro, Davide Montin, Caterina Rizzo, Baldassarre Martire, Michele Miraglia del Giudice and Viviana Moschese
Vaccines 2025, 13(5), 450; https://doi.org/10.3390/vaccines13050450 - 24 Apr 2025
Cited by 16 | Viewed by 11705
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Vaccines for the Vulnerable Population)
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10 pages, 466 KB  
Brief Report
Antibody Response to Pertussis Vaccine Among Children and Adolescents in Croatia: A Cross-Sectional Prevalence Study
by Vedran Stevanović, Oktavija Đaković Rode and Goran Tešović
Vaccines 2025, 13(3), 288; https://doi.org/10.3390/vaccines13030288 - 10 Mar 2025
Cited by 1 | Viewed by 2652
Abstract
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 [...] Read more.
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
(This article belongs to the Section Epidemiology and Vaccination)
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14 pages, 1298 KB  
Article
Impact of DTaP-IPV and DTaP Vaccination Among Adult Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Prospective Observational Study
by Taiichiro Kobayashi, Sho Fujiwara, Ayako Ide, Takashi Toya, Naoki Shingai, Hiroaki Shimizu, Yuho Najima, Takeshi Kobayashi, Noriko Doki and Aoi Jo
Vaccines 2025, 13(3), 275; https://doi.org/10.3390/vaccines13030275 - 5 Mar 2025
Cited by 1 | Viewed by 3116
Abstract
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 [...] Read more.
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
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