DNA Vaccines: Their Formulations, Engineering and Delivery

Vaccines, Год журнала: 2024, Номер 12(1), С. 71 - 71

Опубликована: Янв. 11, 2024

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements augmentation immunogenicity vaccines have brought this technology to market, especially veterinary medicine, prevent many diseases. Along with successful COVID mRNA vaccines, first vaccine for human use, Indian ZyCovD against SARS-CoV-2, approved 2021. In current review, we give an overview focusing on science, including adjuvants and delivery methods. We then cover some emerging science field notably efforts optimize systems, better engineer apparatuses, identify optimal sites, personalize cancer immunotherapy through vaccination, enhance adjuvant gene adjuvants, off-target heritable immunity epigenetic modification, predict epitopes bioinformatic approaches. also discuss major limitations aim address theoretical concerns.

Язык: Английский

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Excess mortality across countries in the Western World since the COVID-19 pandemic: ‘Our World in Data’ estimates of January 2020 to December 2022

BMJ Public Health, Год журнала: 2024, Номер 2(1), С. e000282 - e000282

Опубликована: Май 1, 2024

Introduction Excess mortality during the COVID-19 pandemic has been substantial. Insight into excess death rates in years following WHO’s declaration is crucial for government leaders and policymakers to evaluate their health crisis policies. This study explores Western World from 2020 until 2022. Methods All-cause reports were abstracted countries using ‘Our Data’ database. assessed as a deviation between reported number of deaths country certain week or month 2022 expected that period under normal conditions. For baseline deaths, Karlinsky Kobak’s estimate model was used. uses historical data 2015 2019 accounts seasonal variation year-to-year trends mortality. Results The total 47 3 098 456 1 January 31 December documented 41 (87%) 2020, 42 (89%) 2021 43 (91%) In year onset implementation containment measures, records present 033 122 (P-score 11.4%). 2021, which both measures vaccines used address virus spread infection, highest reported: 256 942 13.8%). 2022, when most lifted continued, preliminary 808 392 8.8%). Conclusions remained high three consecutive years, despite vaccines. raises serious concerns. Government need thoroughly investigate underlying causes persistent

Язык: Английский

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COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Янв. 24, 2024

Our understanding of COVID-19 vaccinations and their impact on health mortality has evolved substantially since the first vaccine rollouts. Published reports from original randomized phase 3 trials concluded that mRNA vaccines could greatly reduce symptoms. In interim, problems with methods, execution, reporting these pivotal have emerged. Re-analysis Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) group. Numerous SAEs were following Emergency Use Authorization (EUA), including death, cancer, cardiac events, various autoimmune, hematological, reproductive, neurological disorders. Furthermore, products never underwent adequate safety toxicological testing accordance previously established scientific standards. Among other major topics addressed this narrative review are published analyses harms to humans, quality control issues process-related impurities, mechanisms underlying (AEs), immunologic basis for inefficacy, concerning trends based registrational data. The risk-benefit imbalance substantiated by evidence date contraindicates further booster injections suggests that, at a minimum, should be removed childhood immunization program until proper studies conducted. Federal agency approval blanket-coverage population-wide had no support an honest assessment all relevant commensurate consideration risks versus benefits. Given extensive, well-documented unacceptably high harm-to-reward ratio, we urge governments endorse global moratorium modified questions pertaining causality, residual DNA, aberrant protein production answered.

Язык: Английский

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mRNA-1273 is placenta-permeable and immunogenic in the fetus

Molecular Therapy — Nucleic Acids, Год журнала: 2025, Номер 36(1), С. 102489 - 102489

Опубликована: Фев. 17, 2025

COVID-19 mRNA vaccines are generally recognized as safe for gestational administration. However, their transplacental pharmacokinetics remain obscure. In this study, mRNA-1273 intramuscularly given to pregnant mice rapidly circulated in maternal blood and crossed the placenta within 1 h spread fetal circulation. Although spike circulation faded away 4-6 h, it could accumulate tissues, mainly liver get translated into protein. Transplacental proved immunogenic fetuses, postnatally equipped with anti-spike immunoglobulin (Ig)M, paternal allotypic IgG2a, heightened cellular immunity. Gestationally administered, had a dose-dependent effect on its transfer immunogenicity higher doses leading increased passage greater serum titers of endogenous IgM/IgG generated by fetuses. Thus, gestationally vaccination might endow newborns not only passive but also active Our results pose new insights capacity potential advancing our knowledge medicine protect unborns against pathogens perinatal life broaden horizons prenatal molecular therapy.

Язык: Английский

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COVID-19 Modified mRNA “Vaccines”: Lessons Learned from Clinical Trials, Mass Vaccination, and the Bio-Pharmaceutical Complex, Part 1

International Journal of Vaccine Theory Practice and Research, Год журнала: 2024, Номер 3(2), С. 1112 - 1178

Опубликована: Июнь 29, 2024

Our understanding of COVID-19 synthetic, modified mRNA (modmRNA) products and their public health impact has evolved substantially since December 2020. Published reports from the original randomized placebo-controlled trials concluded that modmRNA injections could greatly reduce symptoms. However, premature termination both obviated any reliable assessment potential adverse events due to an insufficient timeframe for proper safety evaluation. Following authorization global distribution, problems with methods execution have emerged. The usual testing protocols toxicology requirements were bypassed. Many key trial findings either misreported or omitted entirely published reports. By implication, secondary estimates excess morbidity mortality in must be deemed underestimates. Rigorous re-analyses data post-marketing surveillance studies indicate a substantial degree modmRNA-related harms than was initially reported. Confidential Pfizer documents had revealed 1.6 million by August 2022. A third serious injuries cardiovascular, neurological, thrombotic, immunological, reproductive systems, along alarming increase cancers. Moreover, well-designed shown repeated cause immune dysfunction, thereby potentially contributing heightened susceptibility SARS-CoV-2 infections increased risks COVID-19. This paper also discusses insidious influence Bio-Pharmaceutical Complex, closely coordinated collaboration between organizations, pharmaceutical companies, regulatory agencies. We recommend moratorium on until toxicological are conducted.

Язык: Английский

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Autoimmune inflammatory reactions triggered by the COVID-19 genetic vaccines in terminally differentiated tissues

Autoimmunity, Год журнала: 2023, Номер 56(1)

Опубликована: Сен. 14, 2023

As a result of the spread SARS-CoV-2, global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger suffering serious complications due COVID-19. Solid immuno-histopathological evidence demonstrates that genetic vaccines can display wide distribution within body, affecting tissues are terminally differentiated far away from injection site. These heart brain, which may incur in situ production spike protein eliciting strong autoimmunological inflammatory response. Due fact every human cell synthesises non-self antigens, inevitably becomes target system, since body is not strictly compartmentalised accurate pharmacokinetic pharmacodynamic studies needed order determine precisely be harmed. Therefore, our article aims draw attention scientific regulatory communities critical need for biodistribution against COVID-19, as well rational harm-benefit assessments by group.

Язык: Английский

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Serosurveillance among urban slum and non-slum population immunized with COVID-19 vaccines in Bangladesh

Epidemiology and Infection, Год журнала: 2024, Номер unknown, С. 1 - 34

Опубликована: Янв. 5, 2024

An abstract is not available for this content so a preview has been provided. As you have access to content, full PDF via the 'Save PDF' action button.

Язык: Английский

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Differences in the Evolution of Clinical, Biochemical, and Hematological Indicators in Hospitalized Patients with COVID-19 According to Their Vaccination Scheme: A Cohort Study in One of the World’s Highest Hospital Mortality Populations

Vaccines, Год журнала: 2024, Номер 12(1), С. 72 - 72

Опубликована: Янв. 11, 2024

COVID-19 vaccines primarily prevent severe illnesses or hospitalization, but there is limited data on their impact during hospitalization for seriously ill patients. In a Mexican cohort with high mortality, study assessed vaccination's effects. From 2021 to 2022, 462 patients 4455 hospital days were analyzed. The generalized multivariate linear mixed model (GENLINMIXED) binary logistic regression link, survival analysis and ROC curves used identify risk factors death. results showed that the vaccinated individuals almost half as likely die (adRR = 0.54, 95% CI 0.30-0.97,

Язык: Английский

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mRNA-based therapeutic strategies for cancer treatment

Molecular Therapy, Год журнала: 2024, Номер 32(9), С. 2819 - 2834

Опубликована: Май 3, 2024

Язык: Английский

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Gene therapy in pediatrics – Clinical studies and approved drugs (as of 2023)

Life Sciences, Год журнала: 2024, Номер 348, С. 122685 - 122685

Опубликована: Май 6, 2024

Gene therapy in pediatrics represents a cutting-edge therapeutic strategy for treating range of genetic disorders that manifest childhood. involves the modification or correction mutated gene introduction functional into patient's cells. In general, it is implemented through two main modalities namely ex vivo and therapy. Currently, noteworthy array products has received valid market authorization, with several others various stages approval process. Additionally, multitude clinical trials are actively underway, underscoring dynamic progress within this field. Pediatric fields hematology, oncology, vision hearing loss, immunodeficiencies, neurological, metabolic areas interventions. This review provides comprehensive overview evolution current therapy-based treatments clinic pediatric patients. It navigates historical milestones therapies, currently approved by U.S. Food Drug Administration (FDA) and/or European Medicines Agency (EMA) children, promising future disorders. By providing thorough compilation drugs published results completed ongoing trials, serves as guide clinicians to get quick situation studies 2023.

Язык: Английский

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