scholarly journals Present Situation of Viral Vector Manufacturing and Ways to Overcome Potential Barriers in View of the Routine Large Scale Production and Use of Viral Vectors

Author(s):  
O-W Merten
2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Katharina B. Lauer ◽  
Ray Borrow ◽  
Thomas J. Blanchard

ABSTRACT The presentation and delivery of antigens are crucial for inducing immunity and, desirably, lifelong protection. Recombinant viral vectors—proven safe and successful in veterinary vaccine applications—are ideal shuttles to deliver foreign proteins to induce an immune response with protective antibody levels by mimicking natural infection. Some examples of viral vectors are adenoviruses, measles virus, or poxviruses. The required attributes to qualify as a vaccine vector are as follows: stable insertion of coding sequences into the genome, induction of a protective immune response, a proven safety record, and the potential for large-scale production. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from the same or various pathogens. To protect effectively, some vaccines require multiple antigens of one pathogen or different pathogen serotypes/serogroups in combination (multivalent or polyvalent vaccines). Future multivalent vaccine candidates are likely to be required for complex diseases like malaria and HIV. Other novel strategies propose an antigen combination of different pathogens to protect against several diseases at once (multidisease or multipathogen vaccines).


Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1051
Author(s):  
Eduardo Martínez-Molina ◽  
Carlos Chocarro-Wrona ◽  
Daniel Martínez-Moreno ◽  
Juan A. Marchal ◽  
Houria Boulaiz

Lentiviral vectors (LVs) have gained value over recent years as gene carriers in gene therapy. These viral vectors are safer than what was previously being used for gene transfer and are capable of infecting both dividing and nondividing cells with a long-term expression. This characteristic makes LVs ideal for clinical research, as has been demonstrated with the approval of lentivirus-based gene therapies from the Food and Drug Administration and the European Agency for Medicine. A large number of functional lentiviral particles are required for clinical trials, and large-scale production has been challenging. Therefore, efforts are focused on solving the drawbacks associated with the production and purification of LVsunder current good manufacturing practice. In recent years, we have witnessed the development and optimization of new protocols, packaging cell lines, and culture devices that are very close to reaching the target production level. Here, we review the most recent, efficient, and promising methods for the clinical-scale production ofLVs.


Author(s):  
Sofia Pezoa ◽  
Randall Alfano ◽  
Atherly Pennybaker ◽  
Nathan Hazi ◽  
Andrew Laskowski

Large scale manufacturing of viral vectors or vaccines with adherent cells still relies heavily on the inclusion of fetal bovine serum for the growth and production phases. The inclusion of serum presents numerous problems with the undefined chemical makeup, the undesirable safety profile, and the constraints and limitations on the global supply. Despite these challenges, alternatives to serum for adherent cells have been limited; however, advances in large-scale production of recombinant human proteins have enabled the advancement of blood-free media that can support adherent cell growth. In order to circumvent the need for serum in adherent platforms, we developed a serum and blood-free, chemically defined medium specific for adherent human epithelial kidney cells and evaluated growth kinetics as well as viral vector production with associated adenovirus and lentivirus. We observed doubling times equal to or faster than doubling times observed in serum containing medium. We also demonstrate transfection efficiencies and viral titers that are equivalent to or higher than that of serum. Our results demonstrate that fetal bovine serum is not required for culture of adherent HEK cells, and that a serum-free, blood-free, chemically defined approach can be reliably implemented in the production of viral vectors for gene therapy.


1972 ◽  
Vol 186 (1) ◽  
pp. 281-287
Author(s):  
A. G. Quarrell

Never has the engineer had so many materials from which to choose when designing new machines or new structures. Improved metallurgical knowledge has enabled greatly improved alloys to be developed, the demands of aero-space have stimulated developments in ceramics and in composite materials; whilst advances in organic chemistry have led to a wide range of plastics suitable for applications which range from throw-away containers to constructions for which metals or natural materials were previously used. In addition, improved methods are continuously leading to better materials and more reliable components and the selection of the most suitable process for a given application becomes increasingly difficult. Materials technologists and engineers depend very much on each other. Engineers rely upon materials technologists for materials with properties appropriate for particular applications; materials technologists depend upon engineers to design the machines that enable laboratory experiments to be translated into large-scale production. A review of the present situation will be followed by a discussion of future trends and of future co-operation between engineers and materials technologists.


2015 ◽  
Vol 58 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Afrooz Rashnonejad ◽  
Gholamhossein Amini Chermahini ◽  
Shaoyong Li ◽  
Ferda Ozkinay ◽  
Guangping Gao

1993 ◽  
Vol 32 (1) ◽  
pp. 129-131
Author(s):  
Naureen Talha

The literature on female labour in Third World countries has become quite extensive. India, being comparatively more advanced industrially, and in view of its size and population, presents a pictures of multiplicity of problems which face the female labour market. However, the author has also included Mexico in this analytical study. It is interesting to see the characteristics of developing industrialisation in two different societies: the Indian society, which is conservative, and the Mexican society, which is progressive. In the first chapter of the book, the author explains that he is not concerned with the process of industrialisation and female labour employed at different levels of work, but that he is interested in forms of production and women's employment in large-scale production, petty commodity production, marginal small production, and self-employment in the informal sector. It is only by analysis of these forms that the picture of females having a lower status is understood in its social and political setting.


2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.


2018 ◽  
Vol 15 (4) ◽  
pp. 572-575 ◽  
Author(s):  
Ponnusamy Kannan ◽  
Samuel I.D. Presley ◽  
Pallikondaperumal Shanmugasundaram ◽  
Nagapillai Prakash ◽  
Deivanayagam Easwaramoorthy

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.


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