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The Pediatric Infectious Disease Journal Aug 2023This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and Safety of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T, bOPV, and IPV Vaccines Administered at 2, 4, 6 Months of Age Concomitantly With Rotavirus and Pneumococcal Conjugate Vaccines in Healthy Infants in Thailand.
BACKGROUND
This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine].
METHODS
Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports.
RESULTS
Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group.
CONCLUSIONS
This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines.
Topics: Humans; Infant; Antibodies, Bacterial; Antibodies, Viral; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Hepatitis B; Hepatitis B Vaccines; Immunization Schedule; Poliovirus Vaccine, Inactivated; Rotavirus Vaccines; Thailand; Vaccines, Combined; Vaccines, Conjugate; Pneumococcal Vaccines; Immunogenicity, Vaccine
PubMed: 37257121
DOI: 10.1097/INF.0000000000003975 -
Preventive Medicine Reports Oct 2023Influenza, tetanus, diphtheria, and herpes zoster (HZ) vaccination received within 10 years of the COVID-19 pandemic have been associated with less severe COVID-19...
Influenza, tetanus, diphtheria, and herpes zoster (HZ) vaccination received within 10 years of the COVID-19 pandemic have been associated with less severe COVID-19 infection. We expanded on this evidence to determine if a receiving two different vaccinations (i.e., HZ and tetanus, diphtheria, and pertussis (Tdap)) was associated with a lower risk for COVID-19 hospitalization. De-identified medical record data from a large mid-western health care system was used to determine if, compared to those with neither HZ or Tdap vaccination, patients with either HZ or Tdap and patients with both HZ and Tdap vaccination had lower risk for COVID-19 hospitalization between 4/1/2020 and 12/31/2020. Confounding was controlled using entropy balancing. Patients (n = 363,293) were 71.5 (±8.4) years of age, 57.8% female and 89.2% White race. Prior to controlling for confounding, as compared to patients without either vaccination, those that had either HZ or Tdap were significantly less likely to have a COVID-19 hospitalization (RR = 0.85; 95 %CI: 0.75-0.95). The risk for hospitalization decreased further among those with both HZ and Tdap vaccination (RR = 0.45; 95 %CI:0.28-0.71). After controlling for confounding, including healthy patient bias, receiving both vs. neither vaccinations remained significantly associated with a lower risk of COVID-19 hospitalization (RR = 0.48; 95 %CI: 0.26-0.90). Receiving both Tdap and HZ vaccination is associated with lower risk for COVID-19 hospitalization. Whether there is any benefit of past vaccination exposure in COVID-19 vaccinated patients should be investigated.
PubMed: 37441187
DOI: 10.1016/j.pmedr.2023.102302 -
Current Environmental Health Reports Jun 2024The discovery of per- and polyfluoroalkyl substances (PFAS) in the environment and humans worldwide has ignited scientific research, government inquiry, and public... (Review)
Review
PURPOSE OF REVIEW
The discovery of per- and polyfluoroalkyl substances (PFAS) in the environment and humans worldwide has ignited scientific research, government inquiry, and public concern over numerous adverse health effects associated with PFAS exposure. In this review, we discuss the use of PFAS immunotoxicity data in regulatory and clinical decision-making contexts and question whether recent efforts adequately account for PFAS immunotoxicity in public health decision-making.
RECENT FINDINGS
Government and academic reviews confirm the strongest human evidence for PFAS immunotoxicity is reduced antibody production in response to vaccinations, particularly for tetanus and diphtheria. However, recent events, such as the economic analysis supporting the proposed national primary drinking water regulations and clinical monitoring recommendations, indicate a failure to adequately incorporate these data into regulatory and clinical decisions. To be more protective of public health, we recommend using all relevant immunotoxicity data to inform current and future PFAS-related chemical risk assessment and regulation. Biological measures of immune system effects, such as reduced antibody levels in response to vaccination, should be used as valid and informative markers of health outcomes and risks associated with PFAS exposure. Routine toxicity testing should be expanded to include immunotoxicity evaluations in adult and developing organisms. In addition, clinical recommendations for PFAS-exposed individuals and communities should be revisited and strengthened to provide guidance on incorporating immune system monitoring and other actions that can be taken to protect against adverse health outcomes.
Topics: Humans; Public Health; Risk Assessment; Fluorocarbons; Environmental Exposure; Environmental Pollutants; Immune System; Animals
PubMed: 38526771
DOI: 10.1007/s40572-024-00441-y -
The Journal of Experimental Medicine Oct 2023In this issue of JEM, companion articles from Pinilla et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230104) and Robinson et al. (2023. J. Exp....
In this issue of JEM, companion articles from Pinilla et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230104) and Robinson et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230105) demonstrate that ribotoxic stress induced by Pseudomonas aeruginosa and Corynebacterium diphtheriae EEF2-targeting exotoxins leads to NLRP1 inflammasome activation, representing a new mechanism of effector-triggered immunity.
Topics: Humans; Exotoxins; Inflammasomes; Innate Immunity Recognition; Memory Disorders; NLR Proteins
PubMed: 37642998
DOI: 10.1084/jem.20231160 -
MMWR. Morbidity and Mortality Weekly... Oct 2023In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), the 2021-2030 global strategy that envisions a world where everyone, everywhere, at...
In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), the 2021-2030 global strategy that envisions a world where everyone, everywhere, at every age, fully benefits from vaccines. This report reviews trends in World Health Organization and UNICEF immunization coverage estimates at global, regional, and national levels through 2022 and documents progress toward improving coverage with respect to the IA2030 strategy, which aims to reduce the number of children who have not received the first dose of a diphtheria-tetanus-pertussis-containing vaccine (DTPcv1) worldwide by 50% and to increase coverage with 3 diphtheria-tetanus-pertussis-containing vaccine doses (DTPcv3) to 90%. Worldwide, coverage ≥1 dose of DTPcv1 increased from 86% in 2021 to 89% in 2022 but remained below the 90% coverage achieved in 2019. Estimated DTPcv3 coverage increased from 81% in 2021 to 84% in 2022 but also remained below the 2019 coverage of 86%. Worldwide in 2022, 14.3 million children were not vaccinated with DTPcv1, a 21% decrease from 18.1 million in 2021, but an 11% increase from 12.9 million in 2019. Most children (84%) who did not receive DTPcv1 in 2022 lived in low- and lower-middle-income countries. COVID-19 pandemic-associated immunization recovery occurred in 2022 at the global level, but progress was unevenly distributed, especially among low-income countries. Urgent action is needed to provide incompletely vaccinated children with catch-up vaccinations that were missed during the pandemic, restore national vaccination coverage to prepandemic levels, strengthen immunization programs to build resiliency to withstand future unforeseen public health events, and further improve coverage to protect children from vaccine-preventable diseases.
Topics: Child; Humans; Infant; Vaccination Coverage; Diphtheria; Pandemics; Tetanus; Whooping Cough; Immunization Programs; Vaccination; Diphtheria-Tetanus-Pertussis Vaccine; Immunization Schedule
PubMed: 37883326
DOI: 10.15585/mmwr.mm7243a1 -
AIDS (London, England) Dec 2023Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity...
OBJECTIVE
Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity of data on immune responses to Tdap in pregnant women with HIV (PWWH), and its impact on the protection of their infants has not been described.
METHODS
In an open label phase IV clinical trial in South Africa, we evaluated the immunogenicity and safety of Tdap in PWWH compared with HIV-uninfected women. Antigen-specific immunoglobulin G (IgG) to pertussis toxoid, filamentous haemagglutinin, pertactin, fimbriae, diphtheria and tetanus were measured by electrochemiluminescence-based multiplex assay.
RESULTS
Overall, 91 PWWH and 136 HIV-uninfected pregnant women were enrolled. All PWWH were on antiretroviral treatment and 94.5% had HIV viral loads <40 copies per millilitre. Antibody levels prevaccination were lower among PWWH compared with HIV-uninfected women for all antigens. At 1 month postvaccination PWWH compared with HIV-uninfected women had lower fold-increase and antibody concentrations for all epitopes. Also, a lower proportion of PWWH achieved ≥4-fold increase from pre to postvaccination for pertussis toxoid and pertactin, or diphtheria IgG levels ≥0.1 IU/ml and ≥1 IU/ml postvaccination. Adverse events postvaccination were similar in PWWH and HIV-uninfected.
CONCLUSION
Tdap vaccination was safe and immunogenic. PWHW had, however, attenuated humoral immune responses, which could affect the effectiveness of protecting their infants against pertussis compared with those born to women without HIV.ClinicalTrials.gov identifier: NCT05264662.
Topics: Infant; Female; Humans; Pregnancy; Diphtheria; Tetanus; Whooping Cough; Pregnant Women; HIV; HIV Infections; Diphtheria-Tetanus-acellular Pertussis Vaccines; Vaccination; Immunoglobulin G; Parturition; Antibodies, Bacterial; Immunization, Secondary
PubMed: 37773052
DOI: 10.1097/QAD.0000000000003731 -
Bulletin of the World Health... Apr 2024To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019.
OBJECTIVE
To quantify the association between reduction in child mortality and routine immunization across 204 countries and territories from 1990 to 2019.
METHODS
We used child mortality and vaccine coverage data from the Global Burden of Disease Study. We used a modified child survival framework and applied a mixed-effects regression model to estimate the reduction in deaths in children younger than 5 years associated with eight vaccines.
FINDINGS
Between 1990 and 2019, the diphtheria-tetanus-pertussis (DTP), measles, rotavirus and type b vaccines were significantly associated with an estimated 86.9 (95% confidence interval, CI: 57.2 to 132.4) million fewer deaths in children younger than 5 years worldwide. This decrease represented a 24.2% (95% CI: 19.8 to 28.9) reduction in deaths relative to a scenario without vaccines. The DTP and measles vaccines averted 46.7 (95% CI: 30.0 to 72.7) million and 37.9 (95% CI: 25.4 to 56.8) million deaths, respectively. Of the total reduction in child mortality associated with vaccines, 84.2% (95% CI: 83.0 to 85.1) occurred in 73 countries supported by Gavi, the Vaccine Alliance, with an estimated 45.4 (95% CI: 29.8 to 69.2) million fewer deaths from 2000 to 2019. The largest reductions in deaths associated with these four vaccines were in India, China, Ethiopia, Pakistan and Bangladesh (in order of the size of reduction).
CONCLUSION
Vaccines continue to reduce childhood mortality significantly, especially in Gavi-supported countries, emphasizing the need for increased investment in routine immunization programmes.
Topics: Child; Humans; Infant; Immunization Programs; Vaccination; Measles Vaccine; Child Mortality; Whooping Cough; Measles; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 38562199
DOI: 10.2471/BLT.23.290129 -
Eastern Mediterranean Health Journal =... Sep 2023Every year, WHO and UNICEF estimate the immunization coverage for 195 Member States, based on reported data and independent coverage surveys (1,2). These estimates...
Every year, WHO and UNICEF estimate the immunization coverage for 195 Member States, based on reported data and independent coverage surveys (1,2). These estimates indicate progress in reaching children with life-saving vaccines while identifying coverage gaps (3). The 2022 estimates were much awaited, given that the COVID-19 pandemic caused a setback in coverage (1). Overall, there are encouraging signs of recovery in the WHO Eastern Mediterranean Region (EMR). For example, coverage of the third dose diphtheria-pertussis-tetanus containing vaccine (DTPcv3) and the second dose measles containing vaccine (MCV2), both almost restored or exceeded their 85% and 76% pre-pandemic 2019 levels, respectively (1). However, there are disparities across countries. Low-income countries with fragile, weak health systems and those in conflict situation are lagging. The number of children who missed their routine first dose of measles immunization increased from 3 million in 2019 to 3.16 million in 2022 (1). This underperformance, along with the accumulated immunity gap in 2020-2021, exposes us to the risk of preventable deadly outbreaks.
Topics: Child; Humans; Infant; Pandemics; Immunization Programs; COVID-19; Immunization; Vaccination; Measles Vaccine; Diphtheria-Tetanus-Pertussis Vaccine; Mediterranean Region; Measles; Immunization Schedule
PubMed: 37776128
DOI: 10.26719/2023.29.9.681 -
Frontiers in Immunology 2023The pathogenesis of chronic lung diseases is multifaceted with a major role of recurrent micro-injuries of the epithelium. While several reports clearly indicated a...
INTRODUCTION
The pathogenesis of chronic lung diseases is multifaceted with a major role of recurrent micro-injuries of the epithelium. While several reports clearly indicated a prominent role for surfactant-producing alveolar epithelial type 2 (AT2) cells, the contribution of gas exchange-permissive alveolar epithelial type 1 (AT1) cells has not been addressed yet. Here, we investigated whether repeated injury of AT1 cells leads to inflammation and interstitial fibrosis.
METHODS
We chose an inducible model of AT1 cell depletion following local diphtheria toxin (DT) administration using an iDTR flox/flox (idTR) X Aquaporin 5CRE (Aqp5) transgenic mouse strain.
RESULTS
We investigated repeated doses and intervals of DT to induce cell death of AT1 cells causing inflammation and interstitial fibrosis. We found that repeated DT administrations at 1ng in iDTR X Aqp5 mice cause AT1 cell death leading to inflammation, increased tissue repair markers and interstitial pulmonary fibrosis.
DISCUSSION
Together, we demonstrate that depletion of AT1 cells using repeated injury represents a novel approach to investigate chronic lung inflammatory diseases and to identify new therapeutic targets.
Topics: Mice; Animals; Reinjuries; Mice, Transgenic; Inflammation; Pneumonia; Fibrosis; Cell Death
PubMed: 37841243
DOI: 10.3389/fimmu.2023.1261483 -
Heliyon Dec 2023This study aimed to explore whether acupuncture and moxibustion can enhance the immune response by increasing the expression of the endogenous adjuvant HSP70 mRNA.
OBJECTIVE
This study aimed to explore whether acupuncture and moxibustion can enhance the immune response by increasing the expression of the endogenous adjuvant HSP70 mRNA.
METHOD
Forty Wistar rats were divided into four groups: model immune acupuncture group (A), model immune control group (B), normal immune acupuncture group (C), and normal immune control group (D). Model immune groups A and B were induced by injecting d-galactose for 6 weeks. Rats in groups A and C were then treated with low-frequency electroacupuncture (EA) at Zusanli (ST36), Guanyuan (CV4), and Baihui (GV20) and moxibustion for 3 weeks. Subsequently, all rats were observed for 2 more weeks. At the 12th week, diphtheria antitoxin titers were determined using the Vero cell trace neutralization method, CD4T/CD8T cell ratios in peripheral blood were examined by flow cytometry, and the relative expression of spleen cell HSP70 mRNA was measured by RT-PCR.
RESULTS
Compared with the normal immune control, the diphtheria antitoxin titer, CD4T/CD8T cell ratio, and expression of spleen cell HSP70 mRNA significantly decreased in the model immune control group ( < 0.01). However, the model immune acupuncture group showed a significant increase in antitoxin titer ( < 0.01) and elevated CD4T/CD8T cell ratio and HSP70 mRNA expression ( < 0.05) after EA and moxibustion intervention.
CONCLUSION
Acupuncture and moxibustion may enhance the humoral immune response (diphtheria antitoxin titer) and cellular immune response (peripheral blood CD4T/CD8T cell ratio) by increasing the expression of the endogenous adjuvant HSP70 mRNA, suggesting that acupuncture may serve as a new vaccine adjuvant.
PubMed: 38213597
DOI: 10.1016/j.heliyon.2023.e22645