Diphtheria / Tetanus / Pertussis (acellular component) / Poliomyelitis (inactivated) / Haemophilus type b conjugate vaccine (adsorbed) suspension for injection 0.5ml vials

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.

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Background: Acute lymphoblastic leukemia is the most prevalent childhood cancer and the leading cause of cancer mortality before the age of 20. Although therapeutic advances have significantly improved survival, children and adolescents treated for acute lymphoblastic leukemia remain vulnerable to infections, largely preventable by vaccination, due to humoral and cellular immune dysfunction induced by disease and treatment. Materials and Methods: This systematic review, based on electronic databases, aims to evaluate antibody levels associated with potential protective immunity against vaccine antigens for diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, influenza, varicella-zoster virus, yellow fever, pneumococcal, and meningococcal diseases in children and adolescents treated for acute lymphoblastic leukemia after completion of chemotherapy. Results: A total of twenty-four studies published between 1981 and 2023 were included, comprising 1110 children and adolescents. Protective antibody levels ranged from 11% to 97% for diphtheria, 0% to 90% for pertussis, 20% to 100% for tetanus, and 11% to 95% for poliomyelitis. Haemophilus influenzae type b, protection ranged from 16.7% to 100%. Viral vaccines also showed heterogeneous responses, with protection rates of 25–79% for mumps, 16–86% for measles, 35–98% for rubella, and 23–75% for varicella-zoster virus. Antibody responses to pneumococcal and meningococcal vaccines were consistently low, with protection rates of 5–38% for pneumococcal studies and 12% in a single meningococcal study. Conclusions: This review found a consistent and clinically relevant loss of vaccine-induced immunity in children and adolescents treated for acute lymphoblastic leukemia. The recommendation of vaccine booster doses for this vulnerable population, irrespective of serological status, may represent a more practical approach to ensuring adequate post-chemotherapy treatment protection.

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Low vaccination coverage is highlighted as a challenge in Ukraine and among Ukrainian refugees, however there is limited knowledge on coverage among Ukrainian refugees living in European countries. Individual-level data from the National Population Register for children (<20 years) with at least one parent from Ukraine were linked to the Norwegian Immunisation Registry (SYSVAK). We estimated vaccination coverage according to Norwegian Childhood Immunisation Program recommendations among 1) Ukrainian refugee children (i.e. immigrated after 01.02.2022) (N = 8,804) and 2) children born in Norway to Ukrainian refugee parent(s) (N = 224), compared to national coverage. National coverage rates were 95.8% to 96.5% (2-year-olds), 94.5% to 96.7% (9-year-olds), and 90.0% to 94.0% (16-year-olds). Corresponding rates among Ukrainian refugee children were 39.5% to 60.5%, 27.3% to 58.6%, and 9.2% to 34.3%, respectively. Coverage among Norwegian-born children of Ukrainian refugees was >91%. In all, 31% of Ukrainian refugee children had no vaccinations registered in SYSVAK. Coverage for Human Papilloma Virus (HPV) catch-up vaccination among Ukrainian refugee boys was lowest (9%), however, routine HPV vaccination coverage was 63%. Ukrainian children with a refugee background showed lower vaccination coverage than the national coverage. We found large differences between routine versus catch-up vaccination. Our findings suggest that access to catch-up vaccination, routines for retrospective registration of vaccines given outside of Norway and surveillance reporting, as well as vaccine hesitancy should all be considered when assessing childhood vaccination coverage among Ukrainian refugees. These factors should be addressed to improve vaccine uptake and surveillance in this population.

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Vaccination represents one of the most effective public health interventions. However, a decrease in pediatric vaccination coverage has been observed in Italy, with an increase in vaccine-preventable infectious diseases. To counter this phenomenon, the Italian government approved a compulsory vaccination law in 2017, increasing the number of mandatory vaccinations from four to 10. This study analyzes the trends of vaccination coverages in Italy from 2000 to 2023, with a focus on the impact of the law. Vaccination coverage data were obtained from the Italian Ministry of Health, sorted by antigen. A linear regression and joinpoint regression analysis was performed for each antigen to identify a significant or non-significant change (increase or decrease) in the trend. Vaccination coverages declined steadily until 2015, but with the introduction of the law 119/2017, there was an increase for all antigens, ranging from 1.05% for tetanus to 5.30% for rubella. During the years of the COVID-19 pandemic, a decline in coverage was observed for all antigens, with values ranging from -0.24% for varicella to -2.39% for rubella. Implementing vaccine mandates seem to be useful for increasing vaccination coverages. Likewise, this study showed the negative impact of the COVID-19 pandemic on primary healthcare services, such as vaccination, contributing to a decline in coverage. Health systems should measure vaccination coverages and monitor changes and variations to be resilient toward external stressors and be proactive in tackling crises.

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The DTacP-sIPV/Hib combination vaccine is designed to replace the separate administration of diphtheria, tetanus, acellular pertussis, poliomyelitis, and Haemophilus influenzae type b vaccines. By incorporating Sabin strain inactivated poliovirus, DTacP-sIPV/Hib offers advantages in biosafety and manufacturing cost. This study provides a preliminary evaluation of the preclinical safety of a novel DTacP-sIPV/Hib combination vaccine in three animal models. Sprague-Dawley rats were randomly assigned to receive either DTacP-sIPV/Hib or saline by intramuscular injection and were monitored for 14 days for local reactions, body weight, and food intake, followed by necropsy and histopathological examination. Guinea pigs were allocated to negative control, positive control or vaccine groups and sensitized by three intramuscular injections on alternate days; animals were subsequently challenged and observed for allergic reactions. Japanese white rabbits were used in a bilateral self-controlled design, receiving vaccine in one quadriceps and saline in the contralateral side, with macroscopic and histopathological evaluation at 48 h and 16 days post-injection. The candidate DTacP-sIPV/Hib vaccine induced only mild, transient, and reversible local reactions in SD rats and rabbits, indicating acceptable local tolerability under the conditions tested. No detectable effects on body weight or food intake were observed in rats, and no allergic reactions were induced in guinea pigs, suggesting no apparent systemic safety signals in these models. Overall, these findings provide supportive nonclinical safety evidence for the candidate DTacP-sIPV/Hib vaccine and may inform the design and risk assessment of subsequent clinical studies.

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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 &lt; 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.

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Background: type b (Hib), and DTaP-inactivated polio (IPV)/Hib vaccines has not been thoroughly evaluated in China. Additionally, there are limited data on the VE of acellular pertussis-containing vaccines (aPVs) when used interchangeably. Methods: We conducted a matched case-control study to estimate the VE of aPVs against polymerase chain reaction-confirmed pertussis infection in Lu'an in 2024. A conditional logistic regression model was used to compare the odds ratios (ORs) of vaccination between cases and controls. VE was calculated as [(1 - adjusted OR) × 100%], and 95% confidence intervals (CIs) were computed around the estimates. Results: A total of 1936 children aged 3 months to 16 years were included in the study. The overall VE was 77.3% (95% CI, 35.2%-92.1%). The VE for fully vaccinated children was 88.4% (95% CI, 57.3%-96.8%), while the VE for partially vaccinated children was 77.4% (95% CI, 35.5%-92.1%). The VE of DTaP, DTaP-Hib, and DTaP-IPV/Hib was 75.8% (95% CI, 29.7%-91.7%), 83.2% (95% CI, 47.8%-94.6%), and 79.8% (95% CI, 36.5%-93.6%), respectively. Compared with mixed vaccination (65.3%.), the incremental VE of DTaP, DTaP-Hib, and DTaP-IPV/Hib was 31.0% (95% CI, 1.0%-51.9%), 52.9% (95% CI, 19.1%-72.6%), and 41.1% (95% CI, -18.7% to 71.8%), respectively. We observed a decline in VE over time, decreasing from 76.5% (95% CI, 33.0%-91.7%) within the first 2 years to -5.5% (95% CI, -495.2% to 81.3%) after 6 years or more. Conclusions: All aPVs provide significant protection against pertussis infection, although this protection wanes over time. The VE appears to decrease materially if these vaccines are administered alternately in an individual's routine immunization schedule.

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