Search

Problem definition: The U.S. influenza (flu) vaccine supply chain is decentralized and experiences frequent supply and demand mismatches caused by two key factors: (1) the vaccine production process (yield) is highly uncertain; and (2) individuals are self-interested and do not completely take into account positive and negative externalities that they impose on others. To improve matching of supply and demand, we counteract these factors by developing an ex ante budget-neutral incentive program. Academic/practical relevance: We establish the sources of inefficiency in the flu vaccine supply chain. To eliminate the inefficiency, we develop a two-sided incentive program that policymakers can implement to finance vaccines under an ex ante balanced budget. Methodology: We model the flu vaccine supply chain as a decentralized system consisting of self-interested individuals on the demand side, and a profit-maximizing manufacturer with uncertain yield on the supply side. We use backward induction to characterize the subgame-perfect equilibrium of the sequential game that models the interactions between individuals and the manufacturer. Results: We develop a two-sided incentive program that proposes “vaccination incentives” to be given to individuals on the demand side, and “a menu of transfer payments” between the social planner and manufacturer on the supply side. When the realized vaccine supply is high (or low), our incentive program provides positive (negative) vaccination incentives for individuals to stimulate (or curb) the demand and eliminate positive (or negative) externalities by making vaccination more affordable (or costly). When social benefits from vaccination are significantly high, our incentive program uses a menu of transfer payments to penalize (or subsidize) the manufacturer for low (or high) yield realizations so that it produces the socially optimal quantity. We show that our incentive program can attain the social optimum, maintain an ex ante balanced budget (i.e., budget-neutral in expectation), and distribute the maximum social welfare between individuals and the manufacturer arbitrarily. Managerial implications: Vaccination incentives to individuals can ensure their access to the vaccine, but they are not enough to entice the manufacturer to ensure vaccine availability. A menu of contracts contingent on realized yield provides necessary incentives to the manufacturer and assures the availability.

Vaccines are key in charting a path out of the COVID-19 pandemic. However, development of new vaccines is highly dependent on availability of analytical methods for their design and evaluation. This paper highlights the challenges presented in having to rapidly develop vaccine analytical tools during an ongoing pandemic, including the need to address progressive virus mutation and adaptation which can render initial assays unreliable or redundant. It also discusses the potential of new computational modeling techniques to model and analyze key viral proteins and their attributes to assist vaccine production and assay design. It then reviews the current range of analytical tools available for COVID-19 vaccine application, ranging from in vitro assays for immunogen characterization to assays to measure vaccine responses in vivo. Finally, it provides a future perspective for COVID-19 vaccine analytical tools and attempts to predict how the field might evolve over the next 5–10 years.

The global roll-out of vaccines is crucial to defeating the pandemic, but the lack of technical know-how and manufacturing infrastructure for production are constraining the speedy provision of vaccines globally. This will remain true even if the intellectual property rights of COVID-19 vaccines are waived temporarily. To accelerate technology transfer and global vaccine production, this article calls for the promotion of joint ventures between global COVID-19 vaccine manufacturers and local pharmaceutical companies so as to create regional manufacturing hubs. These joint ventures must be supported financially by global North countries, international organisations, and host-country governments. This approach will incentivize pharmaceutical companies to share not only their patents but also tacit production knowledge because the risk and cost of setting up new facilities will be shared. In this paper, we show how the joint venture approach will have benefits for all the actors involve and generate positive impact on Sub-Saharan Africa and other regions over the long run. Following these policy proposals will not only help protect the global community from COVID-19 but will also present a rare window of opportunity to stimulate the life science industry in the global South, supporting sustainable economic and technological development.

In the 2013-2014 and 2015-2016 seasons, quadrivalent live attenuated influenza vaccine (LAIV) showed reduced pandemic 2009 H1N1 (A/H1N1pdm09) vaccine effectiveness (VE) in the U.S. Impaired fitness of A/H1N1pdm09 LAIV strains in primary human nasal epithelial cells (hNEC) was subsequently shown to be associated with reduced VE. As defective viral genes (DVG) have been detected in QLAIV, it was hypothesised that these might play a role in reduced A/H1N1pdm09 fitness. By applying RT-PCR based approaches, DVG for PB2, PB1 and PA segments were detected in all influenza A LAIV strains tested. Absolute quantification of PA vRNA as a biomarker, using a novel digital RT-PCR assay (RT-dPCR), showed that DVG were a minority population (between 10.2 and 27.8 % of PA vRNA) in LAIV, irrespective of subtype or VE. Importantly, no difference was observed between the fitter pre-2009 H1N1 A/New Caledonia/20/1999 (A/NC99) and less fit A/H1N1pdm09 A/Bolivia/509/2013 (A/BOL13), containing medians of 16.0 % and 10.2 % PA DVG, respectively. Manipulating propagation conditions and minimising A/BOL13 PA DVG to 5.2 % failed to improve viral replication in hNEC, suggesting DVG were not limiting A/BOL13 fitness. Conversely, DVG were able to reduce A/NC99 replication in hNEC to A/BOL13-like levels, but only by enrichment of PA DVG to 66.5 % of vRNA. Notably, this required LAIV propagation under conditions markedly different to those used for vaccine production. We conclude from these data that abundance of DVG in QLAIV is not associated with variations in influenza A VE and that the reduced fitness of A/BOL13 previously described was not driven by the presence of DVG.

Members of the Developing Countries Vaccine Manufacturers’ Network (DCVMN) have been actively engaged in the development of COVID-19 vaccine candidates. According to the WHO COVID-19 vaccine landscape updated on 29 December 2020, 18 member manufacturers had vaccines in preclinical or clinical trials, including three members with candidates in Phase III trials. Once successful candidates have been identified there will be a need for large scale vaccine manufacturing and supply, in which DCVMN member manufacturers can play a key role. In an internal survey in 2019, DCVMN members reported the capability to supply over 3.5 billion vaccine doses annually, and the provision of over 50 distinct vaccines to 170 countries. To describe the capabilities of DCVMN member manufacturers more precisely, a 121-question survey was circulated to 41 Network members. The survey assessed the manufacturers’ capabilities in utilizing various technology platforms, cell cultures and filling technologies, in addition to their capacities for manufacturing drug products. The survey also evaluated manufacturers’ preparedness to dedicate existing capacities to COVID-19 vaccine production. Results revealed that sampled manufacturers have strong capabilities for manufacturing vaccines based on recombinant technologies, particularly with mammalian cells, and microbial and yeast expression systems. Capabilities in utilizing cell cultures were distributed across multiple cell types, however manufacturing capacities with Vero and CHO cells were prominent. Formulating and filling findings illustrated further large-scale capabilities of Network members. Sampled manufacturers reported that over 50% of their capacity for vaccine manufacturing could be dedicated to COVID-19 vaccine production.

A COVID-19 pandemic has erupted around the world. World Health Organization (WHO) and allies are racing to create and deploy safe and effective vaccines as they work together to monitor the pandemic, advise on crucial measures, and distribute essential medical resources to those in need. Vaccines save millions of lives, by training the body's natural defenses, the immune system, to identify and combat the viruses and bacteria they are intended to combat. This review article presents the status of COVID-19 vaccines evaluated by the WHO Emergency Use Listing (EUL) assessment process and those liberated as well. Data was obtained from the WHO, Gavi – The Vaccine Alliance from Bill & Melinda Gates Foundation, Oxford Vaccine Group, Serum Institute of India, AstraZeneca, European Medicines Agency EMA among others. As can be seen, there is still no totally effective vaccine, and many clinical trials are still needed, and even immunized citizens are still at risk of recontagion. Virus mutation is a recurring problem and different vaccine production methodologies are still being studied.

During the first year of COVID-19 pandemic, while there have been rapid developments in diagnosis and treatment of the disease;drug interactions and side effects have created a problem especially in high risk patients with chronic diseases and multiple drug use. In contrast to the routine vaccine production process, SARS-CoV-2 vaccines have been developed in a short period of time by many pharmaceutical companies, and community vaccination has started in many countries. However, this process is restricted by mutation and problems in production and distribution. The fact that the pathophysiology of the disease has not been fully elucidated has brought the prolonged COVID-19 syndrome definition to our clinical practice. Positive improvements and negative aspects that we have encountered so far in the first year of this new pandemic reminded us the great film by Sergio Leone: “The Good, The Bad and The Ugly”. So, we decided to cover these aspects under the same headings. Gaining an overview of the many developments, problems and solution ideas we encountered and witnessed during the pandemic year will make the management of the process easier.

Bu çalışmada yeni bir meta sezgisel optimizasyon yöntemi olan Denge Optimizasyon (DO) algoritması ile aşı üretiminde gerçekleştirilen biyolojik fermantasyon işleminde kullanılan karıştırıcı modelleri için PID kontrolörler tasarlanmıştır. Öncelikle Denge Optimizasyon algoritması PID kontrolör parametrelerini optimize edebilecek kabiliyete ulaştırılmıştır. Daha sonra algoritmanın çalışma performansına etki eden parametrelerde çalışma esnasında deneysel olarak ayarlanmıştır. Özellikle literatürde daha önceden karıştırıcı modelleri için analitik yöntemlerle tasarlanmış olan PID kontrolör yerine performansı daha iyi olan Denge Optimizasyon algoritmasıyla tasarlanmış PID kontrolörlerin kapalı çevrim sonuçları karşılaştırmalı olarak sunulmuştur. Bu sayede yeni bir algoritma olan denge optimizasyon algoritmasının gerçek mühendislik problemlerinde de kullanılabileceği ve analitik yöntemlere karşın daha iyi kontrol performansına sahip PID kontrolörler türetilebileceği gösterilmektedir., In this study, PID controllers are designed for the mixer mathematical models for biological fermentation process in vaccine production with the Equilibrium Optimization (EO) algorithm, which is a new meta-heuristic optimization method. Firstly, Equilibrium Optimization algorithm has been provided with the ability to optimize PID controller parameters. Then, the parameters affecting the working performance of the algorithm were found experimentally during the study. In the literature, the closed loop results of PID controllers designed with the Equilibrium Optimization algorithm, which was previously designed with analytical methods for mixer system, have been presented comparatively. Thus, it is shown that the Equilibrium Optimization algorithm, which is a new algorithm, can also be used in real engineering problems and PID controllers with better control performance can be derived despite analytical methods.

A presente pesquisa possui por Objeto a verificacao da Analise Economica do Direito diante da crise instaurada em âmbito global. Como Objetivo Geral, pretende-se destacar a relevância da Analise Economica do Direito, principalmente ante aos contextos de Crise que despontam esporadicamente tanto nacionalmente, como de forma rara, entretanto preocupante, em nivel global. Como Objetivo Especifico, pretende-se verificar com base na Analise Economica do Direito a notoria guerra fria travada entre os paises a fim de obterem o monopolio da conquista pela producao e propagacao de uma possivel vacina capaz de reverter e curar os impactos da pandemia de virus da COVID-19. Por fim, para a formulacao do presente artigo, foi utilizado o metodo indutivo, partindo-se de diversos posicionamentos ate chegar a um denominador comum, primando pela Humildade Cientifica, instrumentalizado com as tecnicas do Referente, da Categoria, do Conceito Operacional e da Pesquisa Bibliografica. Palavras-chave: Analise Economica da Crise. Vacina. Pandemia. COVID-19. ABSTRACT The purpose of the present research is to verify the Economic Analysis of Law in the face of the crisis that was established globally. As a General Objective, it is intended to highlight the relevance of Economic Analysis of Law, especially in the face of Crisis contexts that emerge sporadically both nationally, and in a rare, however worrying, and global level. As a Specific Objective, it is intended to verify, based on the Economic Analysis of Law, the notorious cold war waged between countries in order to obtain a monopoly on the conquest for the production and propagation of a possible vaccine capable of reversing and curing the impacts of COVID- 19. Finally, for the formulation of this article, the inductive method was used, starting from several positions until reaching a common denominator, striving for Scientific Humility, using the techniques of the Referent, Category, Operational Concept and Research Bibliographic. Keywords: Economic Analysis of the Crisis. Vaccine. Pandemic. COVID-19.

Cell-based vaccine manufacturing is an important strategy for viral disease prevention. Cultivating cells in suspension could maximize the utility of large bioreactors for cost-effective and scaled up vaccine production, where adapting adherent cells to suspension culture is the bottleneck and key. Through whole transcriptome sequencing of suspension and adherent strains of BHK-21 and CHO-K1 cells followed by the identification of differentially expressed genes, mutational analysis, gene ontology, and pathway enrichment analysis, we identified four candidate genes, PABPC1, LARS, GLUL, PFN1, feasible for genetically modulating anchorage-dependent cells toward cell suspension culture, and experimentally validated the functionality of PABPC1 in both BHK-21 and CHO-K1 cells. Our study unveiled a novel role of PABPC1 that could potentially aid in the establishment of a cost-effective vaccine manufacturing platform relying on cell cultivation in suspension.

Özet SARS-CoV-2 (Severe acute respiratory syndrome coronavirus) pandemisi dünya genelinde daha önce benzeri hiç görülmemiş bir aşı talebi oluşturdu. Bu talebi karşılamak için, çok sayıda ticari firma ve kurumsal işletme yeni nesil platform teknolojilerini (mesajcı ribonükleik asit-mRNA ve vektör temelli aşılar) veya geleneksel üretim yaklaşımlarını (subünit ve inaktive aşılar) temel alarak aşı geliştirme çalışmalarına odaklandı. Bu stratejiler arasında mRNA platformunu kullanan bazı aşılar faz III çalışmalarını tamamlayarak birçok ülkede acil kullanım izni aldı ve 2021 yılının ilk günlerinde aşılanan kişi sayısı milyonları aştı. mRNA aşılarının ölçeklenebilir kapasitede, düşük maliyetli ve hızlı üretim avantajlarına rağmen bu yeni teknoloji ile üretim yapan firmalar gelişmiş ülkelerin pandemiye müdahale için talep ettiği birkaç milyar dozu bulan aşı talebine cevap vermekte zorlanmaktadır. Aşı üretim hızını etkileyen en önemli sınırlayıcı faktörlerden biri GMP (Good Manufacturing Practice) koşullarında üretim yapabilen mRNA aşı üretim hatları ile ilgili alt yapının az sayıda ülkede bulunmasıdır. Bir aşı dozunda bulunan RNA miktarı, koruyucu bağışıklama için gereken doz sayısı, bir şişe içerisinde kaç dozluk aşı olduğu, aşı tasarımında modifiye nükleozit kullanılma durumu ve hammadde tedariğindeki sorunlar aşı üretim hızını belirleyen diğer faktörlerdir. Bu süreçte yapılan analizler replike olabilen mRNA aşı tasarımlarının bağışıklama için çok düşük doz (0.1-10 μg) aşı dozu gerektirmesini bu büyük ölçekli talebe verilecek üretim yanıtı etkileyen en önemli parametre olarak değerlendirmektedir. Normal koşullarda aşı üretiminde etkinlik ve güvenlik en önemli ve kritik ölçütler olarak değerlendirilirken, SARS-CoV-2 pandemisinde mRNA aşıları için uzun dönem riskler henüz açıkça ortaya konmamış olmasına rağmen “ölçeklenebilir üretim ve aşı dağıtım altyapısı (soğuk zincir) ile ilgili düzenlemeler” üzerinde daha çok durulmaktadır. Bir diğer önemli adım ise aşıların dağıtımı ve sağlık hizmetleri alt yapısının desteği ile risk gruplarının hızla aşılanmasıdır, ki bazı ülkelerde aşılama sürecinde organizasyon zorlukları yaşandığı gibi soğuk saklama koşullarının yaygın olmadığı bazı ülkelerde ise aşı dağıtımının planlanması gecikmektedir. SARS-CoV-2 pandemisi sürecinde kazanılan tecrübeler ile gelecekteki pandemilere verilecek yanıtın çok daha hızlı, etkili ve kapsamlı olacağı beklenmektedir. Bu makalede mRNA aşılarının üretim ve dağıtımı ile ilgili süreçlerin genel çerçevesi ile özetlenmesi amaçlanmıştır. Abstract The SARS-CoV-2 (Severe acute respiratory syndrome coronavirus) pandemic has created an unprecedented demand for vaccines worldwide. To respond to this demand, many commercial companies and institutional structures focused on vaccine development studies based on next-generation platform technologies (mRNA and vector-based vaccines) or traditional production approaches (subunit and inactivated vaccines).Among these strategies, some vaccines using the mRNA platform completed phase III studies and received emergency validation in many countries, and the number of vaccines exceeded millions in the first days of 2021.Despite the scalable capacity, low cost and fast production advantages of mRNA vaccines, companies that produce with this new technology have difficulty in responding to the vaccine demand, which reaches several billion doses demanded by developed countries for pandemic response.One of the most important limiting factors affecting the speed of vaccine production is that the infrastructure for mRNA vaccine production lines that can produce under GMP (Good Manufacturing Practice) is available in a few countries.The amount of RNA in a vaccine dose, the number of doses required for protective immunization, the number of doses of vaccine in a bottle, the use of modified nucleoside in vaccine design and the problems in raw material supply are other factors that determine the vaccine production rate.Analyzes carried out in this process consider the fact that replicable mRNA vaccine designs require very low dose (0.1-10 μg) vaccine dose for immunization as the most important parameter affecting the production response to this large-scale demand.While efficiency and safety are considered as the most important and critical criteria in vaccine production under normal conditions, although the long-term risks for mRNA vaccines in the SARS-CoV-2 pandemic have not yet been clearly revealed, more emphasis is placed on "regulations regarding scalable production and vaccine distribution infrastructure (cold chain)".Another important step is the distribution of vaccines and the rapid vaccination of risk groups with the support of the healthcare infrastructure. In some countries, organizational difficulties are experienced during the vaccination process and in some countries where cold storage conditions are not common, planning of vaccine distribution is delayed.With the experience gained during the SARS-CoV-2 pandemic process, it is expected that the response to future pandemics will be much faster, more effective, and comprehensive.In this article, it is aimed to summarize the processes related to the production and distribution of mRNA vaccines in a general framework.

During FMD vaccine production, special attention is paid to the concentration of 146S particles bearing the critical biological features of FMDV and being the main components that have an effect on vaccine immunogenicity. For this reason, each batch of vaccine raw material is tested for 146S component concentration. The paper presents the results of the use of a spectrometric method for whole particle concentration determination during quantification of FMDV RNA extracted after immune capture. It is an inexpensive, easy-to-perform method allowing for determination of FMDV 146S particle concentration in the non-inactivated culture suspension. 146S particle concentration was found to depend on the number of RNA molecules extracted from virions after their strain-specific immune capture and quantitatively detected by the spectrometric method. The presented method allows for determination of 146S component concentration in the non-inactivated vaccine raw material using the proposed linear model. The spectrometric method showed 94.5–99.5% correlation with real time reverse transcription polymerase chain reaction and complement fixation test based on the results of tests of 360 non-inactivated suspensions of FMDV of all types. Tests of the positive control demonstrated 99.0–99.6% compatibility of actual and expected results. FMDV genome and 146S particles were not detected in the negative control, and that was in line with expectations.

Clostridium septicum is the causative agent of the acute fetal disease braxy and gas gangrene with major economic losses in the dairy industry. Accurate and rapid detection is great importance in this regard. Vaccination is an effective process for protection against C. septicum infection. It is necessary to identify and evaluate toxigenic Iranian isolates to produce a vaccine. This study aimed to detect Iranian isolates and evaluate toxigenic isolates as candidates for vaccine production. To this end, a total of 17 samples of animals, clinically suspected to braxy and malignant edema, were obtained. All samples were then cultured on media and microbiological and biochemical tests were performed on the colonies. The test results were confirmed by PCR amplification of the alpha-toxin gene. The toxigenic isolates were then evaluated using MLD. The experimental vaccine was produced and evaluated according to the British Pharmacopoeia Standard. According to the results, out of 17 samples, 15 samples were considered C. septicum. All samples were confirmed by PCR amplification. The most toxigenic isolate was used for experimental vaccine production. The result was successful. The Iranian isolate could be, therefore, used for vaccine production although further studies should be conducted in this regard.

Clostridium perfringens is a Gram-positive anaerobic bacterium which is divided based on major toxins into five types (A-E). C. perfringens type D causes fatal enterotoxaemia (pulpy kidney) in sheep and goats that causes heavy economic losses in domestic animals. However current enterotoxaemia vaccine has been effective in controlling of disease; Strategies for the development of effective vaccine can be achieved by the production of new generation experimental vaccines. The aim of this study was cloning and expression of epsilon toxin of C. perfringens type D in E. coli Rosetta (DE3) to improve of the immunity. Epsilon toxin gene was cloned into pJET1.2/blunt vector and pET22b (+) expression vector and finally transformed into E. coli Rosetta competent cells (DE3). The result showed that the epsilon gene of C. perfringens type D can be cloned and expressed in E. coli RosettaTM (DE3) successfully. E. coli was suitable host for the expression of C. perfringens epsilon toxin. Clearly, future research is open for further refinement of the study.

Foot-and-mouth disease virus remains one of the most important livestock diseases in sub-Saharan Africa and several Southeast Asian countries. Vaccination of livestock has been recognized as an important tool for the control of foot-and-mouth disease virus. However, this intervention strategy has some limitations. Generally, vaccine production is a complex multistep process which involves development, manufacturing, and delivery processes, and through this extensive process, some challenges such as poor vaccine storage often arise. More often, these challenges alter the validity of the vaccination. Foot-and-mouth disease virus epidemic dynamics have been extensively explored, but understanding the role of vaccination validity on virus endemicity is lacking. We present a time-delayed foot-and-mouth disease model that incorporates relevant biological and ecological factors, vaccination effects, and disease carriers. We determined the basic reproduction number and demonstrated that it is an important metric for persistence and extinction of the disease in the community. Numerical illustrations were utilised to support some of the analytical results.

Gulobalization promotes changes throughout the world scenario, some not very positive, such as the ease of spreading infectious diseases that threaten global health among different places, which calls for the use of immunization means -see vaccines- so that countries can develop, maintaining health security. The aim of this commentary is to analyze the historical relationship between world well-being and vaccine production. The methodology used was based on studies related to the theme, from 2014-2020, in the languages Portuguese, English and Spanish. The following descriptors were used: vaccines, globalization and health, immunization. This comment is expected to briefly describe the types of vaccines and their importance for maintaining global well-being. Keywords: vaccines, globalization and health, immunization, global health.

The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no approved vaccines or medications exist to prevent infection by SARS-CoV-2. In this emergency, more than 100 vaccines formulated using conventional approaches are being explored against SARS-CoV-2 across the world. The vaccines formulated using nanotechnology are also on the race of clinical trials. The aim of this article is to provide an insight into the ways of vaccine production by conventional and nanotechnology platforms and expand the understanding on the possibilities and limitations of these approaches for vaccine developments.

Coronavirus 19 (COVID-19) pandemic has caused over than 250.000 deaths in world till date. Nearly all countries have taken extraordinary precautions that radically effect life styles, and also serious economical problems have become an important factor in the pandemic process. The world has focused on treatment protocol development and vaccine production studies. Including the two past coronavirus endemics, obesity has been detected to be an important risk factor for many of the acute and chronic diseases. In this study, a systematic review has been planned to determine the relationship between COVID-19 and obesity. For this aim, databases were searched and 390 researches have been determined. Among them 10 (ten) researches meeting criteria have been included in the study. The researches have been done with 6.073 hospitalized COVID-19 patients, and obesity ratio (BMI ≥30) among them differ between 33-75.8%. Obesity has been obtained to be an independent and important risk factor for COVID-19 process in nearly all researches. Further detailed multidisciplinary researches about COVID-19 and obesity will be valuable in the unknown and unpredictable COVID-19 pandemic process.

Introduction: Bacterial ghosts (BGs), known as the empty cell envelope of gram-negative bacteria lacking cytoplasmic content yet retaining all unaltered morphological and structural features of their living counterparts, are widely studied and used as the platform for the production of the vaccines as well as the transporting drug and gene delivery. However, the study related to the creation of BGs based on gene expression is still limited because of the difference in cell wall structure between microorganisms. Therefore, in the current study, for the aims to determine chemicals combination and minimum inhibition concentration (MIC) to optimize BGs production. Material and method: Salmonella choleraesuis strain was collected from NAVETCO company. The study used critical concentrations from chemical combination to convert salmonella cells to BGs. Chemicals combination and MIC, temperature, shaking speed were optimized using Plakett- Burman matrix and response surface methodology. Cell structure was determined by using a scanning electron microscope, experimental mice were vaccinated and challenged with virulence to determine immune responses of bacterial ghost. Results: The appropriate chemicals for the production of BGs biomass were NaOH 3.125 mg/ml; SDS 1.15 mg/ml, H2O2 8.79 µl/ml, ethanol. The observation of morphology, BGs have remained the structure and shape, which were like the living microbial cells. Conclusions: The conditions of BGs production have been identified to produce large amounts of bacterial ghost biomass to further application in vaccine production and pharma.

A serious problem for the development of industrial avian diseases is the emergence of viral diseases, in particular fowl pox virus. Improvement of dysfunctional farms for fowl pox, elimination of foci of pathogens are the most difficult problems facing modern veterinary science and practice. Outbreaks in poultry farms, leading to the need for veterinary and sanitary measures, are a way to protect the poultry from infection on the farm, which is very expensive. In recent years, attempts have been made to improve the means for specific prophylaxis of avian fowl pox diseases. This article describes the widespread use of the cultural vaccine in poultry farming, notes the promise of a cultured cell system, quail embryos, characteristic of economy, the absence of extraneous contaminants, the stability of biological properties, which facilitates the work with them, and is of no small importance in the production of vaccines. The article describes the analysis of the possible cultivation of the strain "Baku". It is also shown that embryos of Japanese origin are more convenient and advantageous tissues for the cultural production of primary cell systems, as well as for biological mass, vaccine production, simplicity, economy, lack of extraneous contaminants and biological properties. It is shown that the culture of the cells of Japanese quail embryos is a promising system for creating highly immunogenic agents that provide special protection against diseases lacking extraneous contaminants and stable biological properties.

The numerous ongoing research programs aimed at finding and producing rapidly an effective anti-coronavirus vaccine require some explanations about the vaccine immunobiology principles. In this article, the fundamental concepts of modern vaccine preparation are summarized and some of the main research initiatives in vaccine production are illustrated. The author hopes that positive results may emerge soon, allowing the solution of the current coronavirus pandemics emerged at the end of 2019 and still ongoing worldwide.

Introduction: Many potential vaccines for COVID-19 are being studied and developed. Several studies have reported on the safety and efficacy of these vaccines. This systematic review aimed to report on the current evidence concerning the feasibility and effectiveness of vaccines for COVID-19. Methods: A systematic search was carried out utilizing the keywords in the online databases, including Scopus, Web of Science, PubMed, Embase, and Cochrane. We included both human and non-human studies because of the vaccine novelty, limiting our ability to include sufficient human studies. Results: This review showed several SARS-CoV-2 vaccines to be currently under development using different platforms, including eight vaccines that are adenovirus-based vectors, six vaccines that are RNA-based formulations, one vaccine being DNA-based formulation, and other vaccines using other platforms, including lipid nanoparticles. Although the safety and efficacy profiles of these vaccines are still under debate, some countries have allowed for emergency use of some vaccines in at-risk populations, such as healthcare workers and the elderly. Conclusion: It is crucial to gather as much clinically relevant evidence as possible regarding the immunogenicity, efficacy, and safety profiles of available vaccines and adhere wisely to CDC protocols and guidelines for vaccine production.

Ticks are increasingly a global public health and veterinary concern. They transmit numerous pathogens that are of veterinary and public health importance. Acaricides, livestock breeding for tick resistance, tick handpicking, pasture spelling, and anti-tick vaccines (ATVs) are in use for the control of ticks and tick-borne diseases (TTBDs); acaricides and ATVs being the most and least used TTBD control methods respectively. The overuse and misuse of acaricides has inadvertently selected for tick strains that are resistant to acaricides. Furthermore, vaccines are rare and not commercially available in sub-Saharan Africa (SSA). It doesn't help that many of the other methods are labor-intensive and found impractical especially for larger farm operations. The success of TTBD control is therefore dependent on integrating all the currently available methods. Vaccines have been shown to be cheap and effective. However, their large-scale deployment for TTBD control in SSA is hindered by commercial unavailability of efficacious anti-tick vaccines against sub-Saharan African tick strains. Thanks to advances in genomics, transcriptomics, and proteomics technologies, many promising anti-tick vaccine antigens (ATVA) have been identified. However, few of them have been investigated for their potential as ATV candidates. Reverse vaccinology (RV) can be leveraged to accelerate ATV discovery. It is cheap and shortens the lead time from ATVA discovery to vaccine production. This chapter provides a brief overview of recent advances in ATV development, ATVs, ATV effector mechanisms, and anti-tick RV. Additionally, it provides a detailed outline of vaccine antigen selection and analysis using computational methods.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented event, and in order to control its spread and minimize its damages, all efforts are immediately mobilized. Mass vaccination is considered a promising solution to combat this universal issue. However, given the urgent need for vaccine production, some of the side effects may not have been presented during trials and will only appear during the mass vaccination. Limited vasculitis cases have been reported so far following vaccination against COVID-19. We present a case of cutaneous leukocytoclastic vasculitis (LCV) induced following the first dose of the ChAdOx1 nCoV-19 vaccine in an otherwise healthy individual.

The novel Coronavirus disease or COVID-19 is a new contagious, dangerous, and deadly viral/immunological systemic disorder with predominantly respiratory features caused by human infection with SARS-CoV-2, which is rapidly spreading from person-to-person all around the world as a pandemic. If the COVID-19 pandemic is not controlled, and then eradicated, it will probably cause the extinction of the human race in the coming years or decades! It shows the fastest multiple genetic mutation for SARS-CoV-2 in the development of the disease. According to the author of this article, an effective vaccine for SARS-CoV-2 will not be made any time soon or may never be made. If it is made, due to the need to use the vaccine several times a year, the staggering cost of vaccine production, its potentially insufficient effect in preventing COVID-19, its possible side effects, and the complexity of its equitable distribution worldwide, it cannot be a significant success in preventing the COVID-19 pandemic. Hence, the only way to eradicate COVID-19 pandemic is: simultaneous, synchronized, and universal quarantine for at least 40 days for all the people of the planet as staying at home for 99% of them and staying at workplace for another 1%, that because of the need for their key job, they need to be present at work. By applying the COVID-19 Referral System for screening people infected with SARS-CoV-2 and Persian Gulf Criteria for diagnosis of COVID-19, we recommend home isolation for mild cases of COVID-19 and hospitalization in Corona Center for severe cases. Also, along with these, more and more SARS-CoV-2 diagnostic tests should be performed using highly sensitive kits, and the principles of prevention of becoming infected with the SARS-CoV-2 should be followed carefully and as soon as possible. By applying all the above, success in controlling and suppressing the SARS-CoV-2 epidemics is anticipated.

Vectored vaccines based on highly attenuated modified vaccinia Ankara (MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken embryo fibroblasts, but production processes based on continuous cell lines emerge as increasingly robust and cost-effective alternatives. An isolate of a hitherto undescribed genotype was recovered by passage of a non-plaque-purified preparation of MVA in a continuous anatine suspension cell line (CR.pIX) in chemically defined medium. The novel isolate (MVA-CR19) replicated to higher infectious titers in the extracellular volume of suspension cultures and induced fewer syncytia in adherent cultures. We now extend previous studies with the investigation of the point mutations in structural genes of MVA-CR19 and describe an additional point mutation in a regulatory gene. We furthermore map and discuss an extensive rearrangement of the left telomer of MVA-CR19 that appears to have occurred by duplication of the right telomer. This event caused deletions and duplications of genes that may modulate immunologic properties of MVA-CR19 as a vaccine vector. Our characterizations also highlight the exceptional genetic stability of plaque-purified MVA: although the phenotype of MVA-CR19 appears to be advantageous for replication, we found that all genetic markers that differentiate wildtype and MVA-CR19 are stably maintained in passages of recombinant viruses based on either wildtype or MVA-CR. Electronic supplementary material The online version of this article (10.1007/s12250-019-00176-3) contains supplementary material, which is available to authorized users.

Process intensification for Peste des Petites Ruminants Virus (PPRV) vaccine production in anchorage dependent Vero cells is challenging, involving substantial amount of bioprocess development. In this study, we describe the implementation of a new, scalable bioprocess for PPRV vaccine production in Vero cells using serum-free medium (SFM), microcarrier technology in stirred-tank bioreactors (STB), in-situ cell detachment from microcarriers and perfusion. Vero cells were successfully adapted to ProVero™-1 SFM, reaching growth rates similar to serum-containing cultures (0.030 1/h vs 0.026 1/h, respectively). An in-situ cell detachment method was successfully implemented, with efficiencies above 85%. Up to 2.5-fold increase in maximum cell concentration was obtained using perfusion when compared to batch culture. Combining perfusion with the in-situ cell detachment method enabled the scale-up to 20 L STB directly from a 2 L STB, surpassing the need for a mid-scale platform (i.e. 5 L STB) and thus reducing seed train duration. Head-to-head comparison of cell growth and PPRV production in the 2 L and 20 L STB was performed, and no significant differences could be observed. Estimated infectious PPRV titers in Tissue Culture Infection Dose (TCID50) (TCID50/mL = 5 × 106 and TCID50/cell = 5) are within the log-range reported in literature for PPRV production in STB and SFM by Silva et al. (2008), thus confirming the feasibility and scalability of the seed train designed [1] . The novel and scalable vaccine production process herein proposed has the potential to assist the upcoming Peste des Petites Ruminants (PPR) Global Eradication Program (targeted by FAAO for 2030) by providing African local and/or regional manufacturers with a platform capable of generating over 25,000 doses of Nigeria 75/1 strain in just 19 days using a 20 L STB.

Live attenuated influenza vaccine (LAIV) is considered one of the most effective vaccines and can be manufactured quickly and inexpensively to counter seasonal or pandemic influenza. Lyophilization is widely used in vaccine production. However, it requires a longer production cycle and large-scale equipment, thus posing a considerable financial burden for developing countries. A potential solution is the development of liquid LAIV, which can increase the yield and reduce the cost of production. In this study, influential factors of LAIV, such as potential stabilizing excipients and pH, were optimized by an orthogonal design. We found that pH is the most critical factor for the stability of LAIV; salt concentration and initial virus titer are also important for LAIV stability. With these data, we developed a liquid formulation consisting of 2.5% sucrose, 0.1% monosodium glutamate, 1% arginine, and 0.5% human serum albumin, with pH ranging from 6.2 to 6.9 (optimum pH 6.5-6.7), for optimal production of monovalent or trivalent LAIVs. This liquid formulation has the potential to considerably improve vaccine production capacity to compensate for the immense shortfall in influenza vaccines globally.

In the event of a pandemic, demand for vaccines may exceed supply. One proposal for allocating vaccines is to use a lottery, to give all citizens an equal chance, either of getting the vaccine (McLachlan) or of surviving (Peterson). However, insistence on strict equality can result in seriously suboptimal outcomes. I argue that the requirement to treat all citizens impartially need not be interpreted to require equal chances, particularly where citizens are differently situated. Assuming that we want to save lives, we should also seek to use vaccine efficiently, so far as this is compatible with equality. Thus, in allocating vaccine, we may want to be sensitive to (i) different levels of need and/or (ii) effects on vaccine production. While such policies may result in unequal chances, they may even improve everyone’s chances. In such cases, the resultant inequality is not a violation of impartiality, but a consequence of considering each person’s claim seriously., Dans le cas d’une pandémie, il est possible que la demande pour des vaccins excède l’offre. Une proposition concernant la distribution des vaccins est d’employer une loterie, afin de donner à tous les citoyens une chance égale soit de recevoir le vaccin (McLachlan) soit de survivre (Peterson). Toutefois, l’accent mis sur une stricte égalité peut produire des résultats gravement sous-optimaux. Je soutiens que l’exigence de traiter tous les citoyens de manière impartiale ne doit pas forcément être interprétée comme une exigence d’égalité des chances, particulièrement en ce qui concerne des citoyens qui sont dans des situations différentes. En supposant que nous voulons sauver des vies, nous devrions également viser à employer les vaccins de manière efficiente, dans la mesure où cela demeure compatible avec l’enjeu d’égalité. Ainsi, notre distribution du vaccin devrait tenir compte de (i) différents degrés de besoin et/ou (ii) des effets sur la production du vaccin. Bien que de telles politiques risquent de conduire à une inégalité des chances, elles peuvent néanmoins améliorer les chances de tous. Dans de tels cas, l’inégalité qui en résulte ne va pas à l’encontre de l’impératif d’impartialité, mais découle plutôt d’une considération sérieuse de la demande de chacun.

The aim of this study is to prepare an applied model for the study of the effect of the economics of vaccine production on health and environment in Egypt, which will achieve the greatest benefit for individuals from the availability of serums and vaccines and the ease of immunization process that provides protection For the individuals. Which impede the production of serums, vaccines and immunization in Egypt . These challenges are the presence of some misconceptions and the lack of awareness of some individuals in the community of the benefits of serums, vaccines and the benefits of immunization in reducing diseases and eradicating them in the beginning before they spread and turn into an epidemic. Destroyed The study examined the concept of serums, vaccines and the difference between each of them in order to know the impact of these challenges on the production of vaccines, immunization and immunization process, and the impact of the immunization process in improving the health of individuals and reducing the spread of diseases and reduce the cases of infections. The study was also based on the analytical method in the practical side based on the answers of the sample of the study and on the study data which was obtained through the survey questionnaire which was distributed to the personnel working in the Holding Company for Biologics and Vaccines (275) 261). The valid questionnaire for the analysis is (250) questionnaire. The survey form is the tool used to achieve the objectives of the study by means of the statistical test of the tests using the statistical program SPSS The study found that there is a statistically significant trend in the economics of serums production and vaccines in Egypt at a significant level of 0.05. There is a statistically significant effect of the production of serums and vaccines on the status of serums and vaccines in health and environment in Egypt at a significant level of 0.05 There is a statistically significant effect for the economics of serums production and vaccines on the status of serums and vaccines in the health and environment in Egypt at a significant level 0.05

— The paper discusses the techniques which are currently implemented for vaccine production based on virus-like particles (VLPs). The factors which determine the characteristics of VLP monomers assembly are provided in detail. Analysis of the literature demonstrates that the development of the techniques of VLP production and immobilization of target antigens on their surface have led to the development of universal platforms which make it possible for virtually any known antigen to be exposed on the particle surface in a highly concentrated form. As a result, the focus of attention has shifted from the approaches to VLP production to the development of a precise interface between the organism’s immune system and the peptides inducing a strong immune response to pathogens or the organism’s own pathological cells. Immunome-specified methods for vaccine design and the prospects of immunoprophylaxis are discussed. Certain examples of vaccines against viral diseases and cancers are considered.

Procedure for validation of the method for indirect assessment of cultural FMD virus titre (T FMDV) in raw materials used for vaccine production with real time reverse transcription polymerase chain reaction (RT-PCRrt) based on determined amplifcation threshold cycle value (Ct) using linear regression model, TFMDV= –0.2956Ct+ 11.4650, is described in the paper. Testing results for 390 samples of cultural FMD virus were analyzed and basic validation characteristics of the proposed method: specifcity, accuracy, precision, limit of detection and limit of quantifcation, application scope and linearity, were defned. Validation results for the method for indirect assessment of FMD virus titre with RT-PCRrt met the acceptance criteria.

Rift Valley Fever (RVF) is an endemic disease in Egypt causing disease in animals and humans since the 1977. Full molecular description of the national vaccine strain is a strategic concern to ensure the antigenic makeup of local vaccine is adequate to provide the required protective immunity for the vaccinated animal species and as a tool of final product quality control. Molecular characterization and phylogenetic analysis of Gc gene of M segment of RVF-ZH501 strain which used in local vaccine production in veterinary serum and vaccine research institute (VSVRI) were carried out in this study. RVF-ZH501 strain was propagated by passages on BHK cell line and then purified my plaque purification technique. RT-PCR for amplification of the Gc gene of M segment. Sequence analysis of the obtained PCR product carried out by MEGA7 program. The result of the study revealed that RVF strain ZH501 Gc genomic content has 99.5 % molecular identity to the strains firstly isolated in Egypt in 1977, so still suitable for vaccine production.

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 spread globally and creates an alarming situation. Following the SARS-CoV-2 paradigm, therapeutic efficacy is achieved via repurposing several antiviral, antibacterial, and antimalarial drugs. Innate and adaptive immune cells work close to combat infection through the intricate production of antibodies (Abs) and inflammatory cytokines. As an essential component of the immune system, Abs play an important role in eliminating viruses and maintaining homeostasis. B lymphocytes (B cells) are effector cells, stringent to produce neutralizing Abs to combat infection. After recognizing SARS-CoV-2 antigens by a surface receptor called B cell receptors (BCRs) on the plasma membrane, the BCRs transmembrane signal transduction and immune activation results in Ab production and development of immune memory. Thus, it ensures that plasma B cells can quickly start an intricate immune response to generate efficient protective Abs to clear the pathogen. Nevertheless, considering therapeutic challenges in the context of the new coronavirus pandemic, this review addresses the molecular mechanism of the immune activation and function of novel SARS-CoV-2 specific B cells in the production of SARS-CoV-2 specific Abs. Additionally, these studies highlighted the Ab-mediated pathogenesis, the intriguing role of nano-scale signaling subunits, non-structural proteins during COVID-19 infection, and structural insights of SARS-CoV-2 specific Abs.

Significance Shortages of COVID-19 vaccines hampered efforts to fight the current pandemic, leading experts to argue for delaying the second dose to provide earlier first-dose protection to twice as many people. We designed a model-based strategy for identifying the optimal second-dose delay using the hospitalization rate as the key metric. While epistemic uncertainties apply to our modeling, we found that the optimal delay was dependent on first-dose efficacy and vaccine mechanism of action. For infection-blocking vaccines, the second dose could be delayed ≥8 weeks if the first-dose efficacy was ≥50%. For symptom-alleviating vaccines, this delay duration is recommended if the first-dose efficacy was ≥70%. These results suggest that delaying the second vaccine dose is a feasible option., Slower than anticipated, COVID-19 vaccine production and distribution have impaired efforts to curtail the current pandemic. The standard administration schedule for most COVID-19 vaccines currently approved is two doses administered 3 to 4 wk apart. To increase the number of individuals with partial protection, some governments are considering delaying the second vaccine dose. However, the delay duration must take into account crucial factors, such as the degree of protection conferred by a single dose, the anticipated vaccine supply pipeline, and the potential emergence of more virulent COVID-19 variants. To help guide decision-making, we propose here an optimization model based on extended susceptible, exposed, infectious, and removed (SEIR) dynamics that determines the optimal delay duration between the first and second COVID-19 vaccine doses. The model assumes lenient social distancing and uses intensive care unit (ICU) admission as a key metric while selecting the optimal duration between doses vs. the standard 4-wk delay. While epistemic uncertainties apply to the interpretation of simulation outputs, we found that the delay is dependent on the vaccine mechanism of action and first-dose efficacy. For infection-blocking vaccines with first-dose efficacy ≥50%, the model predicts that the second dose can be delayed by ≥8 wk (half of the maximal delay), whereas for symptom-alleviating vaccines, the same delay is recommended only if the first-dose efficacy is ≥70%. Our model predicts that a 12-wk second-dose delay of an infection-blocking vaccine with a first-dose efficacy ≥70% could reduce ICU admissions by 400 people per million over 200 d.

Meningococcal disease has been a public health problem in Brazil since the serogroups A and C epidemics occurred in the 1970s. The Oswaldo Cruz Foundation in Brazil has been working to develop a serogroup B meningococcal vaccine composed of detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. Experimental vaccine were produced in a pilot-scale under Good Manufacturing Practice condition (GMP). Physicochemical and biological controls were established based on what has been reported previously for OMV vaccines. The developed vaccine contained the main class 1, 2, 3, and 5 proteins, some minor iron-regulated proteins, and 5–10% residual lipopolysaccharide related to total protein content. The dLOS was added, as a vaccine component, in half of the total protein amount. The pyrogenicity of the final products, based on the residual LOS in OMVs, varied from 1.01 to 2.24 ng LOS/kg rabbit. Three experimental vaccines, were highly immunogenic in mice with better performance using higher antigen concentrations.

The scale-up of animal cell cultivation is important but remains complex and challenging. In the present study, we propose a novel scale-up strategy for baby hamster Syrian kidney-21 (BHK-21) cell cultivation based on similar hydrodynamic environments. The hydrodynamic characteristics of the different scale bioreactors were determined by computational fluid dynamics (CFD) and further correlated with the agitation speed. The optimal hydrodynamic environment for cell cultivation and vaccine production was determined from the cultivation experiments of BHK-21 cells in 5-L laboratory-scale bioreactors equipped with different impellers at various agitation speeds. BHK-21 cell cultivation was scaled up from 5-L to 42-, 350-, and 1000-L bioreactors by adjusting the agitation speed to make the hydrodynamic features similar to those in the 5-L bioreactor, especially for the shear rate in the impeller zone (γimp) and energy dissipation rate in the tank bulk zone (εtan). The maximum cell density and cell aggregation rate in these scaled-up bioreactors were in the range of 4.6 × 106 ~ 4.8 × 106 cells/mL and 16 ~ 20%, which are comparable to or even better than those observed in the 5-L bioreactor (maximum cell density 4.8 × 106 cells/mL, cell aggregation rate 21%). The maximum virus titer of 108.0 LD50/mL achieved in the 1000-L bioreactor was close to 108.3 LD50/mL that obtained in the 5-L bioreactor. Hence, the scale-up strategy proposed in this study is feasible and can efficiently facilitate the scale-up processes of animal cell cultivation.

Millions of people are being vaccinated against SARS-CoV-2 every day, but the virus is also mutating and spreading fast. Vaccine production is increasing, but supply still constrains vaccinations worldwide. Using lower doses of vaccines could dramatically accelerate vaccination. Available evidence on efficacy is not dispositive but suggests half- or even quarter-doses of some vaccines could be almost as effective as currently-used doses. Even if fractional doses are less effective than standard doses, an epidemiological model suggests they could significantly reduce total infections and deaths. The social value of testing dwarfs the costs. However, firms do not internalize the full social value, a market failure that could be addressed with public funding. Governments could support either experimental or observational evaluations of fractional dosing.

UV radiation is highly effective in killing against viruses, bacteria, algae, molds, and yeasts. They are compact, have rapid turn-off and turn-on times, and provide UV radiation at different wavelengths allowing to target specific contaminants. The deep UV LEDs (UVC LEDs) do not contain hazardous substances, such as mercury. Since their operating voltage is low they could be powered by photovoltaic cells. Recent studies have shown that UV radiation at 222 nm is effective in killing viruses but safer for humans compared to 265 nm to 280 nm radiation. Another advantage of UVC LEDs is an ability of rapidly adjust the output power of UVC LED lamps that allows to use the feedback and Artificial Intelligence models to optimize the effects of the UV radiation, save power, and ensure safety. One example, where this is important, is the application of deep UVC LED systems with feedback in vaccine production. A more traditional application of UV LEDs is in water purification being enabled by the recent improvements in deep UV LED power, reliability, packaging, and lifetime. These improvements allow for scaling up the emerging deep UV LED applications and make it feasible to use deep UV LEDs for improving plant yield, extending produce storage time, disinfecting grain and chicken feed, and fighting Hospital Acquired Infections. © COPYRIGHT SPIE. Downloading of the abstract is permitted for personal use only.

Pandemics have a devastating effect on lives across the globe as evinced by the ongoing COVID-19. Production of vaccine, medicines and other critical supplies such as oxygen are indispensable and are to be expedited. This work examines the problem of maximizing the manufacturing of critical supplies within a target stipulated time by various manufacturing units. Two scenarios are considered in vaccine production: centralized and distributed. In the former case, the manufacturing units are closely located and transport the raw materials with no delay. In the latter case, the units are located geographically apart and transport of raw materials takes a finite time causing delays in vaccine production. The main contribution of the paper lies in the elucidation of optimal algorithms for both scenarios that take the dependencies between the ingredients into consideration. The dependencies have a constraining effect on the order of manufacturing of both the raw materials and the end products referred to as targets and hence careful consideration is necessary to maximize production. The optimality is measured by an incentive-based scheme that seeks to reward the faster development of targets.

Data are available to promote the advancement of biotechnological resources to counter this novel epidemic of Coronavirus. This paper discusses and analyzes the significant applications of artificial intelligence and machine learning to the regular operations of the COVID-19 outbreak. Continued advancement in artificial intelligence and machine learning has improved care, medication, screening, prediction, contact detection, and drug/vaccine production approaches for the COVID-19 flu pandemic and reduced human interventions in medical practice. However, several models have not been applied enough to illustrate their real-world operation, but they also display promising results in the battle against the COVID-19 virus.

Malaria is a worldwide scourge, and the broad deployment of an effective vaccine would improve the lives of millions of people. A vaccine based on Plasmodium falciparum (PfSPZ) sporozoites extracted from the salivary glands of infected mosquitoes shows significant promise. However, the large-scale industrial production of PfSPZ-based vaccines will benefit from automation of the key step of extracting sporozoites from mosquito salivary glands that is currently performed by manual microdissection. In this work, we demonstrate a robotic system prototype for extracting salivary glands from mosquitoes to streamline vaccine production and reduce the need for operators. In the proposed system, mosquitoes are decapitated in an automated robotic pick-place-decapitate process, then a squeezer apparatus extracts mosquito salivary glands from the body. Mosquito detection and body part localization are performed by computer vision methods. The software allows system operation in simulation and on the robotic hardware, which facilitates subsystem development and integration. Experiments show encouraging results with success rates of 93% in robotic mosquito manipulation and 87.1% in salivary gland extraction. The system has the potential to improve the efficiency of PfSPZ vaccine production with significant gains in throughput and reduction in training times for a highly deskilled initial manual step. Further, this system is expected to pave the way for a more mature future system.

Recently, India is at risk due to the exponential rising of COVID-19 infection, which generated a second wave. This infection rise may affect the vaccination program in India, and it can also affect vaccine production. In this manuscript, we have discussed the psychosocial and political factors that have driven the current wave of India. We have also tried to depict the psychosocial and political obstacles that are impairing the vaccination program.

COVID-19 has created a pandemic situation all over the world. It has spread in nearly every continent. Researchers all over the world are trying to produce an effective vaccine against this virus, however; no specific treatment for COVID-19 has been discovered -so far. The current work describes the inhibition study of the SARS-CoV-2 main proteinase or 3CL Mpro by natural and synthetic inhibitors, which include 2S albumin and flocculating protein from Moringa oleifera (M. oleifera) and Suramin. Molecular Docking study was carried out using the programs like AutoDock 4.0, HADDOCK2.4, patchdock, pardock, and firedock. The global binding energy of Suramin, 2S albumin, and flocculating proteins were −41.96, −9.12, and −14.78 kJ/mol, respectively. The docking analysis indicates that all three inhibitors bind at the junction of domains II and III. The catalytic function of 3CL Mpro is dependent on its dimeric form, and the flexibility of domain III is considered important for this dimerization. Our study showed that all three inhibitors reduce this flexibility and restrict their motion. The decrease in flexibility of domain III was further confirmed by analysis coming from Molecular dynamic simulation. The analysis results indicate that the temperature B-factor of the enzyme decreases tremendously when the inhibitors bind to it. This study will further explore the possibility of producing an effective treatment against COVID-19.

Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model. The qualitative methodology identifies and assesses the direction, magnitude and shape of the impact of critical process parameters (CPPs) on critical quality attributes (CQAs). The mechanistic bioprocess model quantifies and maps the effect of four CPPs on the CQA of effective yield of RNA drug substance. Consequently, the first design space of an RNA vaccine synthesis bioreactor is obtained. The cost-yield optimization together with the probabilistic design space contribute towards automation of rapid-response, high-quality RNA vaccine production.