Production, testing and perspectives of IPV and IPV combination vaccines: GSK biologicals' view

Duchêne, Michel

doi:10.1016/j.biologicals.2006.03.010

Cited by 20 publications

(8 citation statements)

References 5 publications

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“…HeLa (human cervical carcinoma) cell line is a standard laboratory model for growing poliovirus. Vero (African green monkey kidney) cell line is also widely used in poliovirus research and is an approved cell line for high-yield commercial poliovirus propagation for vaccine production (29). First, we characterized poliovirus growth in both cell lines.…”

Section: Resultsmentioning

confidence: 99%

Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

Viktorova

Nchoutmboube

Ford-Siltz

2015

J Virol

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It is hypothesized that targeting stable cellular factors involved in viral replication instead of virus-specific proteins may raise the barrier for development of resistant mutants, which is especially important for highly adaptable small (؉)RNA viruses. However, contrary to this assumption, the accumulated evidence shows that these viruses easily generate mutants resistant to the inhibitors of cellular proteins at least in some systems. We investigated here the development of poliovirus resistance to brefeldin A (BFA), an inhibitor of the cellular protein GBF1, a guanine nucleotide exchange factor for the small cellular GTPase Arf1. We found that while resistant viruses can be easily selected in HeLa cells, they do not emerge in Vero cells, in spite that in the absence of the drug both cultures support robust virus replication. Our data show that the viral replication is much more resilient to BFA than functioning of the cellular secretory pathway, suggesting that the role of GBF1 in the viral replication is independent of its Arf activating function. We demonstrate that the level of recruitment of GBF1 to the replication complexes limits the establishment and expression of a BFA resistance phenotype in both HeLa and Vero cells. Moreover, the BFA resistance phenotype of poliovirus mutants is also cell type dependent in different cells of human origin and results in a fitness loss in the form of reduced efficiency of RNA replication in the absence of the drug. Thus, a rational approach to the development of host-targeting antivirals may overcome the superior adaptability of (؉)RNA viruses. IMPORTANCECompared to the number of viral diseases, the number of available vaccines is miniscule. For some viruses vaccine development has not been successful after multiple attempts, and for many others vaccination is not a viable option. Antiviral drugs are needed for clinical practice and public health emergencies. However, viruses are highly adaptable and can easily generate mutants resistant to practically any compounds targeting viral proteins. An alternative approach is to target stable cellular factors recruited for the virus-specific functions. In the present study, we analyzed the factors permitting and restricting the establishment of the resistance of poliovirus, a small (؉)RNA virus, to brefeldin A (BFA), a drug targeting a cellular component of the viral replication complex. We found that the emergence and replication potential of resistant mutants is cell type dependent and that BFA resistance reduces virus fitness. Our data provide a rational approach to the development of antiviral therapeutics targeting host factors. M orbidity and mortality associated with positive-strand RNA [(ϩ)RNA] viruses represent a significant public health burden worldwide. Vaccines are available for some of these viruses, such as poliovirus, hepatitis A virus, yellow fever virus, and a few others, and yet in most cases for the diseases induced by (ϩ)RNA viruses modern medicine can offer nothing more than supportive therapie...

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Section: Resultsmentioning

confidence: 99%

Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

Viktorova

Nchoutmboube

Ford-Siltz

2015

J Virol

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“…These methods increase the possibility of error in the experimental data. Other viral vaccines also have similar problems (19,20). Therefore, an in vitro approach based on the measurement of the antigen content of the vaccine as a surrogate marker of the PRN titer has been successfully applied for some viral vaccines in recent years.…”

Section: Discussionmentioning

confidence: 99%

Development of an in vitro antigen‐detection test as an alternative method to the in vivo plaque reduction neutralization test for the quality control of Japanese encephalitis virus vaccine

Kim

et al. 2012

Microbiology and Immunology

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Japanese encephalitis virus (JEV) causes diseases that attack the human central nervous system. Traditionally, the quality control for JEV vaccines, in which the plaque reduction neutralization (PRN) titer is measured by the national control laboratories before the vaccine batches are marketed, has required laboratory animal testing. However, classical animal tests have inherent problems, including the very fact that animals are used, ethical issues, and the possibility of error. In this study, JEV antigen was measured in an in vitro assay to assess the feasibility of replacing in vivo assays that measure the PRN titers of JEV vaccines. We constructed a double‐sandwich enzyme‐linked immunosorbent assay (DS‐ELISA) that could detect JEV envelope (E). Initially, monoclonal antibodies (mAbs) directed against the JEV E protein were generated and characterized. We isolated 18 mAbs against JEV E protein, and most were the IgG1 or IgG2a isotype. The mAbs (5F15 and 7D71) were selected as the most suitable mAb pair to detect JEV E protein. DS‐ELISA with this pair detected as little as approximately 3 μg/mL JEV E protein and demonstrated a relationship between the amount of JEV E protein and the PRN titer. From these results, we surmise that this DS‐ELISA may be useful, not only in terms of measuring the amount of JEV E protein, but also as a substitute for the PRN test for JEV vaccine evaluation.

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“…Hence, new polio vaccine manufacturing facilities must be capable of compliant operation at the BSL-3 level for the foreseeable future insofar as no date for a cessation of IPV use, which is envisioned minimally to provide coverage through the immediate post eradication period of 3-5 years, is fixed [31][32][33][34][35][36][37]. Furthermore, with manufacturing costs for inactivated polio vaccine 20-fold higher than for OPV (OPV), [40][41][42][43] it will be important to further optimize the manufacturing process for the inactivated vaccine, especially for use in developing countries. Furthermore, with manufacturing costs for inactivated polio vaccine 20-fold higher than for OPV (OPV), [40][41][42][43] it will be important to further optimize the manufacturing process for the inactivated vaccine, especially for use in developing countries.…”

Section: Basis For a Standard Vaccine Facility Design Platformmentioning

confidence: 99%

“…As a result, as IPV will replace oral polio vaccine (OPV) over the next years and in the future be the only acceptable vaccine for prevention of polio [38] demand for IPV will reach skyward to the order of 450 million doses five times higher than the current global manufacturing capacity for the inactivated viral vaccine, today's existing manufacturing capacity for the inactivated polio vaccine is insufficient to meet the needs for this vaccine [39]. Furthermore, with manufacturing costs for inactivated polio vaccine 20-fold higher than for OPV (OPV), [40][41][42][43] it will be important to further optimize the manufacturing process for the inactivated vaccine, especially for use in developing countries. The optimized manufacturing process and cell substrate recently published by Crucell [44,45] could help to reduce the manufacturing costs of the inactivated vaccine while the flexible, modular facility we describe here will ensure that sufficient manufacturing capacity for this vaccine could be built at an economically viable cost and made available in a short time period.…”

Section: Basis For a Standard Vaccine Facility Design Platformmentioning

confidence: 99%

Paradigm shift for vaccine manufacturing facilities: The next generation of flexible, modular facilities

Pralong

Levine²,

Lilja³

et al. 2014

Engineering in Life Sciences

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Most vaccines today are manufactured using technologies developed 40–50 years ago, often in facilities of similar antiquity, resulting in complex, uncharacterized products with relatively high production costs. As a result, the vaccine industry today is struggling to meet the challenges of improving existing products and developing new vaccines for unmet medical needs at an economical cost. The unique nature of each vaccine manufacturing process makes it difficult to develop standard platform processes and facility designs similar to those used in antibody manufacturing. While no single facility or process can meet the requirements of all vaccines, we have developed a new paradigm for vaccine manufacturing facilities which exploit the emergence and full acceptance of single use technologies, modern engineering and design concepts, and capabilities of modular construction. Modularization of facility design and construction and the application of single use technologies permit rapid construction and commissioning of vaccine facilities while significantly reducing the capital and operational expenditures required for such facilities. Using inactivated polio vaccine as a model, we present a new design concept which can be rapidly deployed in different locations adapted to market and/or tender strategies without incurring the risk or cost of excess process architecture and drug product changes.

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Production, testing and perspectives of IPV and IPV combination vaccines: GSK biologicals' view

Cited by 20 publications

References 5 publications

Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

Development of an in vitro antigen‐detection test as an alternative method to the in vivo plaque reduction neutralization test for the quality control of Japanese encephalitis virus vaccine

Paradigm shift for vaccine manufacturing facilities: The next generation of flexible, modular facilities

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