Proteomics Technology Applied to Upstream and Downstream Process Development of a Protein Vaccine (original) (raw)
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Proteomics for development of vaccine
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The success of genome projects has provided us with a vast amount of information on genes of many pathogenic species and has raised hopes for rapid progress in combating infectious diseases, both by construction of new effective vaccines and by creating a new generation of therapeutic drugs. Proteomics, a strategy complementary to the genomic-based approach, when combined with immunomics (looking for immunogenic proteins) and vaccinomics (characterization of host response to immunization), delivers valuable information on pathogen-host cell interaction. It also speeds the identification and detailed characterization of new antigens, which are potential candidates for vaccine development. This review begins with an overview of the global status of vaccinology based on WHO data. The main part of this review describes the impact of proteomic strategies on advancements in constructing effective antibacterial, antiviral and anticancer vaccines. Diverse aspects of disease mechanisms and disease preventions have been investigated by proteomics.
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Infectious diseases still remain the main cause of human premature deaths, especially in developing countries. Vaccines constitute the most cost-effective tool for prophylaxis of infectious diseases. Elucidation of the complete genomes of many bacterial pathogens has provided a new blueprint for the search of novel vaccine candidates. At the same time, it was a turning point in the development of transcriptomics and proteomics. This article concentrates on the proteomic contribution to vaccinology, pointing out relationships between genomic, transcriptomic and proteomic approaches and describing how they complement one another. It also highlights the recent proteomic techniques applied to antigen identification, their capabilities and limitations, as well as the strategies that are taken to overcome technical difficulties and to refine applied methods. Finally, some recent experimental data concerning the proteomic/immunoproteomic influence on identification of vaccine candidates to prevent human infections caused by Streptococcus spp., as well as by a major bioterrorist agent, Bacillus anthracis is presented.
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The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to demonstrate safety, potency, and purity. To date, production processes have either not been disclosed or are bench-scale in nature and cannot be readily adapted to clinical and commercial scale production. To address these needs, we have advanced an aqueous-based scalable process that is readily adaptable to GMP-compliant manufacturing, and developed the required analytical methods for product characterization, quality control release, and stability testing. We also have demonstrated the products produced at manufacturing scale under such approaches display good potency and protection in relevant animal models with mRNA products encoding both vaccine immunogens and antibodies. Finally, we discuss continued challenges in raw material identification, sourcing and supply, and the cold chain requirements for mRNA therapeutic and vaccine products. While ultimate solutions have yet to be elucidated, we discuss approaches that can be taken that are aligned with regulatory guidance.
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The use of biological systems to synthesize complex therapeutic products has been a remarkable success. However during product development great attention must be devoted to defining acceptable levels of impurities that derive from that biological system, heading this list are host cell proteins (HCPs). Recent advances in proteomic analytics have shown how diverse this class of impurities is; as such knowledge and capability grows inevitable questions have arisen about how thorough current approaches to measuring HCPs are. The fundamental issue is how to adequately measure (and in turn monitor and control) such a large number of protein species (potentially thousands of components) to ensure safe and efficacious products. A rather elegant solution is to use an immunoassay (ELISA) based on polyclonal antibodies raised to the host cell (biological system) used to synthesize a particular therapeutic product. However, the measurement is entirely dependent on the antibody serum used, whi...
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Live attenuated and inactivated pathogens, as well as subunit vaccinations, can give long-term protection against a variety of deadly diseases. Despite this progress, vaccine development for a number of infectious diseases, particularly those that are more capable of evading the adaptive immune response, remains a serious issue. Furthermore, the fundamental impediment to the greatest uptake of virus vaccines isn’t usually the efficacy of conventional procedures, but rather the requirement for more fast research and large-scale manufacture. As a result, the development of more powerful and adaptable vaccine platforms is critical. The complexities of developing the manufacturing process, formulation, and analytical assays, as well as the problem of scientific assay optimization, are the most well-known barriers to vaccine development failures or delays. Scientists argue that the extremely concentrated state of global vaccine manufacturing capacity limits large-scale vaccine production...
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The successful development of vaccines is a lengthy process, requiring input from different expertises, such as research and development, quality control, quality assurance, production, regulatory affairs, and marketing and sales. A cornerstone in vaccine development is the availability of a panel of high-quality assays that can reduce the risk of failure in clinical trials and licensure. This review highlights the quality-control issues and approaches in vaccine development from different viewpoints: discovery, process development, assay development, clinical development and the postlicensing phase.
A Brief Review of Computer-Assisted Approaches to Rational Design of Peptide Vaccines
International Journal of Molecular Sciences, 2016
The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages. The developments in bioinformatics, proteomics, immunogenomics, structural biology and other sciences have spurred the growth of vaccinomics where computer assisted approaches serve to identify suitable peptide targets for eventual development of vaccines. In this mini-review we give a brief overview of some of the recent trends in computer assisted vaccine development with emphasis on the primary selection procedures of probable peptide candidates for vaccine development.
2008
D evelopment and manufacturing of recombinant-protein–based vaccines has in the past few years become very similar to that of other well-documented and well-characterized biological drugs. For investigational vaccines, chemistry, manufacturing, and controls (CMC) information is critical for a successful regulatory filing. The process development and CGMP manufacturing of a recombinant protein drug is on the critical path toward clinical phase 1 dosing and safety studies as well as proof-of-concept clinical studies (1, 2). However, resources invested in this process may be wasted if the methods and results are not sufficiently documented. Here we describe how proteomics technology has enabled a scientific, risk-based framework for implementing process analytical technology (PAT) in the development of a well-characterized protein vaccine. Our aim is to identify the scientific tools that support innovation in process development and to exemplify the strategy for regulatory implementati...
Comparability of biotherapeutics: characterization of protein vaccine antigens
Pharmaceutical Bioprocessing, 2013
Advances in biotechnology and analytical tools now permit the application of extensive analytical characterization packages to purified recombinant proteins, a significant progression from the traditional characterization of complex biological products primarily by their manufacturing process. In this article, the authors focus on comparability assessment of biotherapeutics, specifically vaccine protein antigens. Regulatory drivers and analytical approaches used to examine product comparability are discussed and two case studies are described in detail to demonstrate the comparability of pre-and post-change product at the early and late stages of vaccine development. In coming years the number of comparability studies will likely increase due to the greater number of vaccine manufacturers, production at multiple sites and with external partners, and the introduction of innovative process technologies. Comparability studies may be focused on only a few changes, or may be more extensive, to address the impact of multiple process changes at various stages of manufacturing.