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Increasing production capacity may necessitate the facility to cater for higher hazardous area category (e.g., H-Occupancy) design features, such as specialized building construction and potential blast zones. [...]an assessment should cover: * Quantification of flammable material use for production steps, including buffer preparation and LNP storage * Equipment and facility cleaning strategies that contribute to the facility flammable materials inventory * Impact of HVAC design to avoid hazardous atmospheres (e.g., full fresh air), use of local exhaust ventilation (LEV) or fume hoods * Solvent distribution methods (e.g., closed solvent delivery and waste removal systems) * Location of solvent bulk storage outside of the processing area/ facility, and piping in what is necessary plus removing spent solvent in a timely manner (e.g., piped transfer to a waste tank for removal by a specialist contractor). At present, the process cannot be fully single-use, so thought needs to be put into the cleaning and sterilization processes, plus the analytical support infrastructure needed for reusable product-contact surfaces. [...]it is recommended that for each mRNA project, consideration is given to the following aspects to determine the link between the equipment available and the facility design: * Need for custom/proprietary equipment * Independent production rooms with "through-wall" buffer transfer through iris ports in from logistics corridor (Buffer Prep/Hold) * Room electrical classification needs versus process step. * Equipment selection versus electrical and fire code requirements * Benefits and limitations of implementing single-use technologies, given that the process will be hybrid (with stainless steel). [...]the limited capacity for outsourcing of supporting functions, such as facility environmental monitoring or product sterility testing, should be considered during concept design.
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According to expert opinion, the incorporation of effective adjuvants that can trigger both mucosal and systemic immune responses are necessary for noninvasive vaccine delivery, and a more extensive understanding of mucosal immunity is required (4). To overcome these potential issues, it has been suggested by some experts that gelling agents, such as polymers, included in the formulation could increase the residence time of the vaccine in the nasal passage (5). Another potential intranasal candidate from Altimmune is no longer in development as a result of inadequate immune response in healthy volunteers (8).
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Telma Lery Janssen EMEA therapeutic area lead for infectious diseases and vaccines at Johnson & Johnson, explains that the company's COVID-19 vaccine candidate (also known as Ad26.COV2.S, Ad26COVS1, VAC31518, JNJ-78436735, or Ad26-S.PP) is a monovalent, recombinant, inactivated/non-infective adenovirus vector (similar to a cold virus), which contains a transgene that codes for the coronavirus spike (S) protein. The vaccine technology, AdVac, is based on the development and production of adenovirus vectors (gene carriers). Adenovirus vectors (gene carriers) are genetically altered forms of an adenovirus and lack the DNA needed to replicate. Some of the main differences between a COVID-19 oral tablet vaccine from injectable COVID-19 vaccines, according to Tucker, include: * Immune responses are triggered in the mucosa and the serum with a COVID-19 oral tablet vaccine (based on preclinical and clinical testing), unlike the existing vaccines that are serum-only. * Ease of distribution and vaccination with a COVID-19 oral tablet vaccine, which eliminates the need for special accommodations to transport injectable vaccines that require cold chain infrastructure as well as the need for trained professionals to administer vaccines.
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The long-term trend is for development of allogeneic cellular and gene therapies, involving batched manufacturing of products to be used for treatment of multiple patients (1). There is potential for a significant shortage of manufacturing capacity-measured as total volume of bioreactors in use-particularly at commercial scales, similar to a decade or more ago when there was widespread expectation of a severe shortage of capacity for mainstream recombinant products. [...]reflecting the primitive state of much cellular/gene therapies bioprocessing, only 16% each cited, "Our commercial manufacturing will or does use only closed systems, aseptic transfers/connections, etc." and "Anticipate no problems with meeting good manufacturing practice (GMP) requirements."
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The COVID-19 pandemic has accelerated the need for modular designs to rapidly expand vaccine production capacity. Speed to market An established benefit of modular facilities is that they are constructed off-site and then delivered to the site where they will be put into use. CRB's SlateXpace was introduced in September 2020 as a "suitebased" modular facility design for cell and gene therapy. Modular systems enable the manufacturer to produce regionally on the required scale and thus to react flexibly to the current situation and local requirements," says Kappeler.
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Numerous advantages to inhalation vaccines Vaccines delivered via inhalation enable targeting of the respiratory tract mucosa and generation of both humoral and cell-mediated immunity, according to Pierre A. Morgon, executive vice president. [...]inhaled vaccines delivered as liquids using nebulizers can potentially be administered with lower requirement for extensive healthcare infrastructure or as many trained healthcare personnel within an immunization centre (2). Researchers at McMaster University, for instance, have shown inhalation of a tuberculosis vaccine to be more effective than delivery via nasal sprays, because the vaccine penetrates much deeper into the airway (8). Because inhaled vaccines provide local immunity to the respiratory tract, they are seen to be ideal solutions for interrupting the spread of viruses with high transmission rates and the potential to lead to global pandemics (9). Beyond these two approaches, there are inhalation vaccines under development based on attenuated influenza virus, parainfluenza virus (PIV) 5, lentiviruses, Newcastle disease virus (NDV), and vesicular stomatitis virus (VSV);bacterium vectors, nucleic acids (messenger RNA, DNA), and protein subunits (3).
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Challenges with traditional vaccines The potential exists for adverse effects because live viral vaccines are attenuated by genetic mutation of the wild-type, disease-causing virus, either by passaging the virus through cells, eggs, or animals or purposeful deletion of sections of the viral genome, explains Kelly Lyn Warfield, vice president of vaccines research and development within Emergent BioSolutions' Vaccines Business Unit. "For selection and use of live, attenuated viral vaccines, caution must be applied due to potential safety issues in immunocompromised individuals (i.e., primary immunodeficiencies, patients on immunosuppressant treatment, HIV-infected people, and sometimes the very young or old), since this type of vaccine has the potential to replicate in an uncontrolled manner. spread to other individuals due to shedding of the vaccine, or revert to a virulent (disease-causing) form," she says. [...]a viral vector-based vaccine can cause an immune response to the viral vector itself in addition to the antigen of interest for which it is delivering the nucleic acid, according to Gregory Bleck, vice president of research and development at Catalent Biologies. [...]to achieve complete immune protection and to increase its duration, a prime boost dosing regimen in two consecutive vaccinations with the same or a different vaccine may be applied, which is what we're seeing in the mRNA COVID-19 vaccines," he says.
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Coronavirus disease 19 (COVID-19) mRNA vaccines sometimes cause various skin rashes. We report an unusual case of erythema nodosum-like nodules with vesicular and pustular papules, which arose after the first shot of a COVID-19 mRNA vaccine. A skin biopsy showed marked neutrophilic infiltration with necrobiotic changes throughout the dermis and subcutis. Immunohistochemically, CD8+ cells were much more common than CD4+ cells in the dense neutrophilic infiltrates. Many CD68+ macrophages were present around the CD8+ cells. No cases of neutrophilic dermatosis with necrobiotic changes have been reported. Thus, our findings should be added to the cutaneous adverse effects of the vaccines.
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28 Figure 1a) Frequency of a detectable antibody response after each vaccination for 80 heart transplant recipients, b) Interval change in anti-spike antibody titres between the 2nd ChAdOx1 nCoV-19 vaccine and the 3rd dose mRNA (BNT162b2) booster vaccine.[Figure omitted. See PDF]Conclusions/ImplicationsHeart transplant recipients who received 2 doses of the ChAdOx1 nCoV-19 viral vector vaccine and a mRNA booster vaccine failed to develop a detectable antibody response in 44% of cases. These findings highlight the importance of maintaining protective measures for transplant recipients, particularly those on more intensive immunosuppressive regimens, both at a personal and public health level, as well as investigating additional strategies to protect this vulnerable patient cohort.
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Introduction: Recently, capillary leak syndrome (CLS) emerged as new suspected adverse event after immunization (AEFI) associated to COVID-19 vaccination. This condition is rare, but serious and potentially fatal [1]. Objective: Our pharmacovigilance study aims to evaluate the onset of CLS as AEFI with COVID-19 mRNA vaccines (Spikevax and Comirnaty) compared to viral vector vaccines (Janssen and Vaxzevria). Methods: We carried out descriptive and disproportionality analyses of all Individual Case Safety Reports (ICSRs) reporting a vaccine COVID-19 as suspected drug and the CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. For the disproportionality analysis we applied the Reporting Odds Ratio (ROR) 95% CI. Results: During study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19, Vaxzevria®, (N = 36) and Janssen®, (N = 9), while the ICSR reported to vaccines COVID-19 mRNA were 39 (Comirnaty®, N = 33;Spikevax®, N = 6). Majority of ICSRs were reported by healthcare professionals (N = 60;71.4%). The non-healthcare professional represented the primary source in the 41.7% of Vaxzevria® related ICSRs. Majority of the patients were adult (N = 49;58.3%). The female gender accounted in more than 65% of ICSRs referred both to mRNA and viral vector vaccines. The CLS outcome was more frequently favorable in mRNA ICSRs (N = 13;33,3%). On the other hand, among the ICSRs reporting CLS with unfavorable outcome (N = 25;29.8%) we found 9 ICSRs describing fatal CLS (Comirnaty® N = 1;Vaxzevria® N = 4;Janssen® N = 4). From disproportionality analysis emerged a lower CLS reporting probability after COVID-19 vaccination with mRNA vaccines compared to viral vector-based ones. Conclusion: According to our results, few ICSRs describing CLS have been collected in EV in front of billion administered doses. This could underline the rarity of this AEFI or the limit of underreporting of spontaneous reporting and therefore also our study. Since the significant clinical relevance of CLS, this AEFI requires a careful monitoring. Healthcare professionals as well as patients should be aware of the signs and symptoms of CLS. Patients with a history of CLS require particular attention because of a possible risk of flare-up of disease. Since a precise mechanism is still not identified, further studies are necessary to confirm the causal relationship between CLS and COVID-19 vaccination.
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Introduction: COVID-19 is a complex disease with several clinical phases of progression, affecting many organs apart from the respiratory tract that has shown a worst prognosis in both patients with type 1 and type 2 diabetes mellitus [1]. Based on these considerations, the vaccination for COVID-19 is a priority for this subpopulation [2]. However, few data have been published on the effects of impaired glucose metabolism induced by COVID-19 vaccines. Objective: We decided to perform a study to describe Individual Case Safety Reports (ICSRs) of impaired glucose metabolism events reported in the European database (Eudravigilance, EV). Methods: ICSRs were retrieved for the period from January 1st, 2021 to December 11th, 2021. An ICSR related to events of impaired glucose metabolism was identified by using selected preferred terms (PTs) from Standardized MedDRA Queries "Hyperglycaemia/new onset diabetes mellitus" and "Hypoglycaemia". Impaired glucose metabolism events were described and analyzed based on the Diabetologists' classification into nine groups: "diabetes in pregnancy", "acute complications of diabetes", "pre-diabetes", "type 1 diabetes mellitus", "type 2 diabetes mellitus", "high glucose levels", "diabetes mellitus inadequate control", "diabetes melli-tus not specified", and "hypoglycaemia". The reporting odds ratios were computed to assess the reporting frequency for COVID-19 mRNA vaccines compared to COVID-19 viral vector-based vaccines. Results: During the study period, 3,917 ICSRs with a COVID-19 vaccine as suspected and at least an event of impaired glucose metabolism were retrieved from the EV, of which 2,027 (51.75%) referred to Pfizer-BioNTech vaccine, 586 (14.96%) to Moderna vaccine, 1,163 (29.70%) to Oxford-AstraZeneca vaccine, and 141 (3.59%) to Janssen vaccine. From 3,917 ICSRs, we observed 4,275 impaired glucose metabolism events (1.09 adverse events per ICSR). Most adverse events were classified as serious (2,694;63.02%), and the most reported events were related to "high glucose levels" (2,012;47.06%). The mRNA vaccines were associated with an increased reporting frequency of "type 1 diabetes mellitus" (ROR 1.86;95% CI 1.33-2.60), "type 2 diabetes mellitus" (ROR 1.58;95% CI 1.03-2.42), "high glucose levels" (ROR 1.16;95% CI 1.06-1.27), "diabetes mellitus inadequate control" (ROR 1.63;95% CI 1.25-2.11), and "hypoglycemia" (ROR 1.62;95% CI 1.41-1.86) compared to viral vector-based vaccines. The highest reporting rate per 100,000 was observed for Oxford-AstraZeneca vaccine (1.87;95% CI 1.77-1.97). Conclusion: In conclusion, mRNA COVID-19 vaccines were associated with an increased reporting frequency of alterations of glucose homeostasis compared to viral-vector COVID-19 vaccines. Clinicians should be aware of these events to better manage glycaemic perturbations. Larger nationwide studies are warranted to verify these findings.
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Introduction: During large-scale vaccination campaign against COVID-19, the Italian Medicines Agency (AIFA) in collaboration with the Regional Centres of Pharmacovigilance have carried out a closely monitoring of Individual Case Safety Reports (ICSRs) about Adverse Event Following Immunisation (AEFIs) related to COVID19 vaccines and have assured a constant communication through public monthly reports1. During the first months of the vaccination campaign, a signal of rare events of thrombosis associated with thrombocytopenia2, particularly in young women, was detected by health authorities associated with the viral vector vaccines ChAdOx1S S Ad26.COV2-S. Objective: To present a comprehensive assessment of thrombotic and thromboembolic events associated with thrombocytopenia following COVID-19 immunisation with viral vector vaccines recorded in the Italian National Pharmacovigilance Network database Methods: We selected all ICSRs reported from 27 December 2020 to 26 December 2021 containing Preferred Terms (PT) related to platelet count reduction associated with PT related to thrombotic and thromboembolic events (clinical symptoms and/or diagnostic tests). All cases of thrombotic and thromboembolic events reporting thrombocytopenia in the narrative description of the report were also reviewed. The selected ICRSs were submitted to the independent evaluation of three pharmacovigilance experts who blindly classified into 5 levels of diagnostic certainty, according to the definition provided by the Brighton Collaboration Group (BCG)3. Disagreement were resolved by plenary discussion. Results: 12,166,236 doses of ChAdOx1-S and 1,500,746 of Ad26.COV2-S have been administered in Italy during the considered interval with overall 23,358/117,947 ICSRs related to ChAdOx1-S (19.8 %) and 1,580/117,947 related to Ad26.COV2-S (1.3 %). A total of 134 reports after vaccination with adenoviral vaccines were identified according to the inclusion criteria, of which 107 cases were defined as thrombotic thrombocytopenia (95 following ChAdOx1-S and 12 after Ad26.COV2-S). 27 reports were defined as "not case" (level 5, Brighton) on the basis of clinical examination or investigation, or because of the presence of heparin as a concomitant drug. Furthermore, 3 reports were excluded because of a hereditary thrombophilia or a previous history of other thrombotic episodes. Seventy-seven cases were classifiable as BCG levels 1, 2, and 3 (definite, probable and possible cases, respectively) with an overall reporting rate at about 1 case per approximately 200,000 doses administered. Women aged 30 to 49 years showed the highest reporting rates. Conclusion: In Italy, the rates of thrombotic thrombocytopenia following COVID-19 immunisation with viral vector vaccines are in line with those reported in other Countries.
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The frequency of reported symptoms was higher in: the younger (<40 years) age group, those who had taken two doses, and participants with a history of adverse reaction to a medicine/vaccine. Keywords: Nigeria * COVID-19 * Oxford-AstraZeneca * ChAdOx1 nCoV-19 * Adverse effects * Vaccine Introduction The widespread morbidity and mortality associated with the 2020 COVID-19 pandemic precipitated the most extensive and rapid global vaccine development program in history, culminating in several vaccine candidates attaining phase 3 efficacy milestones and receiving emergency use authorization by the end of the same year [1,2]. Using a confidence interval of 95%, a 6% margin for error, and allowing for 10% no-response rate, the minimum sample size was determined to be 296 by Cochran formular. Ethical approval This study was approved by the Health Research Ethics Committee of Bingham University Teaching Hospital, Jos, Plateau State.
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As malaria cases continue to decline in Asia, an integrated service delivery approach is ever more urgent to ensure that no malaria and fever cases are missed, and that malaria health workers continue contributing to broader infectious disease control efforts. However, despite its perceived merit, translating integrated surveillance into practice poses several systemic challenges. This article aims to identify what is hindering improved processes for integrating diagnostic and surveillance services for febrile illnesses. Data from peer‐reviewed and grey literature were reviewed using a systems approach based on the World Health Organisation health systems building blocks to fully understand the connections between different elements and system implications of integration. We include snippets from Sri Lanka, Myanmar, Malaysia and Nepal, highlighting expanded diagnostic integration best practices. This review provides a foundation for ‘integration roadmaps’ that can be adapted to different contexts and guide national stakeholders on the operational and political steps for a successful integration model. Such a model can support malaria elimination efforts and serve as a public health tool in the context of disease surveillance and regional health security.
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A national 2017 vector control capacity survey was conducted to assess the United States’ (U.S.’s) ability to prevent emerging vector-borne disease. Since that survey, the southeastern U.S. has experienced continued autochthonous exotic vector-borne disease transmission and establishment of invasive vector species. To understand the current gaps in control programs and establish a baseline to evaluate future vector control efforts for this vulnerable region, a focused needs assessment survey was conducted in early 2020. The southeastern U.S. region was targeted, as this region has a high probability of novel vector-borne disease introduction. Paper copies delivered in handwritten envelopes and electronic copies of the survey were delivered to 386 unique contacts, and 150 returned surveys were received, corresponding to a 39% response rate. Overall, the survey found vector control programs serving areas with over 100,000 residents and those affiliated with public health departments had more core capabilities compared to smaller programs and those not affiliated with public health departments. Furthermore, the majority of vector control programs in this region do not routinely monitor for pesticide resistance. Taken as a whole, these results suggest that the majority of the southeastern U.S. is vulnerable to vector-borne disease outbreaks. Results from this survey raise attention to the critical need of providing increased resources to bring all vector control programs to a competent level, ensuring that public health is protected from the threat of vector-borne disease.
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Introduction. The purpose of the work was to determine the antiviral and bactericidal action of the steam-water mixture containing ozone created by the POS-1 apparatus on models of the transmissible gastroenteritis virus of pigs of the coronavirus family and multi-resistant clinical strains of bacteria, as well as the selection of optimal parameters for the supply of ozone in the composition of the gas mixture, which does not cause pathological changes on the part of organs and body systems. Materials and methods. To create a gas mixture containing ozone, the POS-1 apparatus created by the team of NMC Medinteh LLC was used. Virological studies were conducted on the basis of the Institute of Epidemiology and Infectious Diseases named after L.V. Gromashevsky. As a working material, models of the vector-borne gastroenteritis virus of pigs of the coronavirus family were used. A series of bacteriological and experimental studies were performed on the basis of the State Institution of the National Institute of Surgery and Transplantology named after A.A. Shalimov of the National Academy of Medical Sciences of Ukraine. For bacteriological studies, polyresistant cultures at a concentration of 108 CCU/ml were used. To study the effects of an ozone-containing mixture of gases on living biological tissues, studies on white rats were performed in the experiment. Results. Virological studies have shown that at an exposure of 20 minutes in contact with an extracellular virus, the infectious titer decreased by 100,000 times, and at an exposure of 30 minutes, complete deactivation of the virus occurred. Bacteriological studies revealed a complete absence of culture growth after treatment with an ozone-containing mixture for 20 minutes. The results of swimming tests and behavioral reaction of white rats of the control and experimental groups did not differ from each other. Histological studies of the tissues of the respiratory system, as well as the spleen, thyroid gland, kidneys and adrenal glands did not reveal signs of pathological effects. Conclusions. 1. The parameters of ozone generation and supply in the composition of the steam-water mixture of gases were studied and optimally selected. 2. Studies of the effect of the ozone-containing mixture on the strain of the virus of the coronavirus family, as well as bacteriological studies on multi-resistant clinical bacterial cultures confirm the pronounced virocidal and bactericidal properties of the developed method. 3. The use of an ozone-containing mixture does not cause any pathological changes on the part of the organs and systems of a living organism. 4. The gas mixture can be used to prevent and treat infectious diseases of the respiratory system, both viral and bacterial genesis.
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From our study, all three covid-19 vaccines have a similar proportion of adverse reaction reports in which the patient had a history of allergies. However, the proportion of life-threatening outcomes were lower for those with the Janssen vaccine (0.62% hospitalization rate for Janssen versus 2.59% for Pfizer and 0.60% death for Janssen versus 5.15% for Moderna). In terms of specific allergies, patients with ·cillin or sulfa allergies had the most adverse reactions to covid-19 vaccines, however, Janssen again had the lowest percentage of reported deaths (1.39% for ·cillin-related allergy deaths for Janssen versus 6.10% for Pfizer). In terms ofpatient age and gender, females has 2.9x the number of adverse reactions than males and a lower average age for reactions for the Pfizer and Moderna vaccines. We feel this data could be used by individuals and medical professionals to assist in choosing a vaccine to maximize patient safety based on their allergy history, age and gender.