New international guidance on quality, safety and efficacy of DNA vaccines.
Ontology highlight
ABSTRACT:
SUBMITTER: Beasley DWC
PROVIDER: S-EPMC7303182 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Consultations have been held to promote the revision of the WHO guidelines for assuring the quality and nonclinical safety evaluation of DNA vaccines adopted by the Expert Committee on Biological Standardization (ECBS) in 2005. The drivers for this revision are described, including the need for regulatory convergence highlighted by the WHO R&D Blueprint. These consultations have driven the revision to its current form, where a new guideline that includes quality, nonclinical, and clinical evaluation of plasmid DNA vaccines is being prepared for public consultation with a view to present to an upcoming ECBS. Major changes to the guidelines include streamlining the existing quality (part A) and nonclinical (part B) sections to reflect the two decades of experience, with manufacturing and control, nonclinical evaluation, and clinical testing of plasmid DNA vaccines, as a platform technology. The urgency for gaining regulatory convergence on this topic is that development of such a platform technology as DNA vaccines for routine use immunizations will prepare manufacturers and regulators across the globe in dealing with rapid development of medical countermeasures against emerging infectious diseases even in the face of an emergency setting. Two examples are described of Zika candidate vaccines that have rapidly advanced in development based on preexisting nonclinical and clinical data that precluded the need to repeat nonclinical toxicology. This report describes the progress stemming from the most recent consultation on the guidelines, including topics discussed and consensus reached.
| S-EPMC7303131 | biostudies-literature
Project description:Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.
| S-EPMC8662238 | biostudies-literature
Project description:Despite many years of research, human DNA vaccines have yet to fulfill their early promise. Over the past 15 years, multiple generations of DNA vaccines have been developed and tested in preclinical models for prophylactic and therapeutic applications in the areas of infectious disease and cancer, but have failed in the clinic. Thus, while DNA vaccines have achieved successful licensure for veterinary applications, their poor immunogenicity in humans when compared with traditional protein-based vaccines has hindered their progress. Many strategies have been attempted to improve DNA vaccine potency including use of more efficient promoters and codon optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime-boost strategies. This review summarizes these advances in DNA vaccine technologies and attempts to answer the question of when DNA vaccines might eventually be licensed for human use.
| S-EPMC3293989 | biostudies-literature
Project description:Surgical innovations have made enormous contributions towards the welfare of patients when they have been appropriate, effective and applied with expertise and overall care. However, the potential for advancement and for harm of new surgical techniques, and the level of expertise necessary for their safe introduction, are not always immediately apparent. Furthermore, it is difficult and time-consuming to assess the efficacy and safety of new procedures in the clinical setting. In 1998 the Royal Australasian College of Surgeons established ASERNIP-S, the Australian Safety and Efficacy Register of New and Interventional Procedures-Surgical, to help ensure that new technologies that are being introduced are well proven in concept, are as safe and effective as possible, and are utilized with high levels of skill underpinned by the level of training.
| S-EPMC2225509 | biostudies-other
Project description:We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine.
| S-EPMC4409070 | biostudies-literature
Project description:The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccine-induced AIDS deaths). We use our framework to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs. We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact. We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe.
| S-EPMC30702 | biostudies-literature
Project description:Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18) responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11) which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease.
| S-EPMC4470159 | biostudies-literature
Project description:Due to their rapid and widespread development, DNA vaccines have entered into a variety of human clinical trials for vaccines against various diseases including cancer. Evidence that DNA vaccines are well tolerated and have an excellent safety profile proved to be of advantage as many clinical trials combines the first phase with the second, saving both time and money. It is clear from the results obtained in clinical trials that such DNA vaccines require much improvement in antigen expression and delivery methods to make them sufficiently effective in the clinic. Similarly, it is clear that additional strategies are required to activate effective immunity against poorly immunogenic tumor antigens. Engineering vaccine design for manipulating antigen presentation and processing pathways is one of the most important aspects that can be easily handled in the DNA vaccine technology. Several approaches have been investigated including DNA vaccine engineering, co-delivery of immunomodulatory molecules, safe routes of administration, prime-boost regimen and strategies to break the immunosuppressive networks mechanisms adopted by malignant cells to prevent immune cell function. Combined or single strategies to enhance the efficacy and immunogenicity of DNA vaccines are applied in completed and ongoing clinical trials, where the safety and tolerability of the DNA platform are substantiated. In this review on DNA vaccines, salient aspects on this topic going from basic research to the clinic are evaluated. Some representative DNA cancer vaccine studies are also discussed.
| S-EPMC2846346 | biostudies-literature
Project description:Assessing the groundwater quality at a Saudi Arabian agricultural site and the occurrence of antibiotic-resistant opportunistic pathogens on irrigated food produce
| PRJEB9501 | ENA
Project description:The numbers of cases and deaths from coronavirus disease 2019 (COVID-19) are continuously increasing. Many people are concerned about the efficacy and safety of the COVID-19 vaccines. We performed a comprehensive analysis of the published trials of COVID-19 vaccines and the real-world data from the Vaccine Adverse Event Reporting System. Globally, our research found that the efficacy of all vaccines exceeded 70%, and RNA-based vaccines had the highest efficacy of 94.29%; moreover, Black or African American people, young people, and males may experience greater vaccine efficacy. The spectrum of vaccine-related adverse drug reactions (ADRs) is extremely broad, and the most frequent ADRs are pain, fatigue, and headache. Most ADRs are tolerable and are mainly grade 1 or 2 in severity. Some severe ADRs have been identified (thromboembolic events, 21-75 cases per million doses; myocarditis/pericarditis, 2-3 cases per million doses). In summary, vaccines are a powerful tool that can be used to control the COVID-19 pandemic, with high efficacy and tolerable ADRs. In addition, the spectrum of ADRs associated with the vaccines is broad, and most of the reactions appear within a week, although some may be delayed. Therefore, ADRs after vaccination need to be identified and addressed in a timely manner.
| S-EPMC8342868 | biostudies-literature