Process Development for Newcastle Disease Virus-Vectored Vaccines in Serum-Free Vero Cell Suspension Cultures

Fulber, Julia Puppin Chaves; Farnós, Omar; Kießlich, Sascha; Yang, Zeyu; Dash, Sanjit Kumar; Susta, Leonardo; Wootton, Sarah K.; Kamen, Amine

doi:10.3390/vaccines9111335

Cited by 17 publications

(26 citation statements)

References 45 publications

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“…VERO cells are derived from African green monkey kidney and act as hosts for ERV and SARS-CoV-2, which is a good model for this study. VERO cells are also widely used in the study of the molecular mechanism of virus infection, as well as the production of vaccines and recombinant proteins, and are regarded as an ideal cell model for cultivating influenza vaccines and studying the molecular mechanism of virus infection [ 60 , 61 , 62 ]. VERO cells could not secrete interferon α/β when infected with a virus because of their inherent genetic defects.…”

Section: Discussionmentioning

confidence: 99%

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Guo

Yang

Liu

et al. 2022

Viruses

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Background. Interferon is a marker of host antiviral immunity, which is disordered in COVID-19 patients. ERV can affect the secretion of interferon through the cGAS-STING pathway. In this study, we explored whether IFN-I and HERV-K (HML-2) were activated in COVID-19 patients and whether there was an interaction between them. Methods. We collected blood samples from COVID-19 patients and healthy controls. We first detected the expression of HERV-K (HML-2) gag, env, and pol genes and IFN-I-related genes between patients and healthy people by qPCR, synchronously detected VERO cells infected with SARS-CoV-2. Then, the chromosome distributions of highly expressed HERV-K (HML-2) gag, env, and pol genes were mapped by the next-generation sequencing results, and GO analysis was performed on the related genes. Results. We found that the HERV-K (HML-2) gag, env, and pol genes were highly expressed in COVID-19 patients and VERO cells infected with SARS-CoV-2. The interferon-related genes IFNB1, ISG15, and IFIT1 were also activated in COVID-19 patients, and GO analysis showed that HERV-K (HML-2) can regulate the secretion of interferon. Conclusions. The high expression of HERV-K (HML-2) might activate the increase of interferon in COVID-19 patients, proving that HERV-K does not only play a negative role in the human body.

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Section: Discussionmentioning

confidence: 99%

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Guo

Yang

Liu

et al. 2022

Viruses

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“…Aside from safety and efficacy, NDV also offers versatility when it comes to production processes. This virus has been produced extensively in embryonated chicken eggs [ 31 , 38 ] and has also shown the capacity of infecting continuous cell lines such as HEK293 [ 3 ], Vero [ 3 , 20 , 39 ], DF-1 [ 20 , 38 , 40 ], MDCK [ 41 ] and HeLa [ 42 ]. Although there are very few studies focusing on process development for NDV, it shows the potential to be produced in either egg-based or cell culture-based processes depending on which production facilities are available and which strategies are adopted.…”

Section: Characteristics Of Ndv As a Viral Vectormentioning

confidence: 99%

“…Viral vectors are typically produced in ECEs or cell culture, from which they are harvested and purified for vaccine formulation ( Figure 2 ). NDV has been extensively produced in ECEs for poultry vaccination and for pre-clinical studies, with only a few studies propagating this virus in cell lines ( Table 1 and Table A1 ) and, to our knowledge, only four studies producing it in lab-scale bioreactors [ 3 , 100 , 101 , 102 ].…”

Section: Manufacturing Of Ndv-vectored Vaccinesmentioning

confidence: 99%

“…The pipeline to develop and manufacture new vaccines became a global concern, leading to significantly more resources being leveraged into this field [ 2 ]. With this increased demand comes a need for the development and optimization of vaccine platforms—technologies that can rapidly be adapted to target an emerging disease, with minimal changes to the manufacturing process [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, there are very few studies exploring the production of NDV in cell culture, which could be scaled to bioreactor production facilities. Cell culture-based processes provide several advantages over production in eggs: they avoid issues with allergens, eliminate dependence on chicken egg supply, and allow greater control over each operation parameter, which leads to more reproducibility, scalability and optimization of the process [ 3 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Development and Scalable Production of Newcastle Disease Virus-Vectored Vaccines for Human and Veterinary Use

Fulber

Kamen

2022

Viruses

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The COVID-19 pandemic has highlighted the need for efficient vaccine platforms that can rapidly be developed and manufactured on a large scale to immunize the population against emerging viruses. Viral-vectored vaccines are prominent vaccine platforms that have been approved for use against the Ebola virus and SARS-CoV-2. The Newcastle Disease Virus is a promising viral vector, as an avian paramyxovirus that infects poultry but is safe for use in humans and other animals. NDV has been extensively studied not only as an oncolytic virus but also a vector for human and veterinary vaccines, with currently ongoing clinical trials for use against SARS-CoV-2. However, there is a gap in NDV research when it comes to process development and scalable manufacturing, which are critical for future approved vaccines. In this review, we summarize the advantages of NDV as a viral vector, describe the steps and limitations to generating recombinant NDV constructs, review the advances in human and veterinary vaccine candidates in pre-clinical and clinical tests, and elaborate on production in embryonated chicken eggs and cell culture. Mainly, we discuss the existing data on NDV propagation from a process development perspective and provide prospects for the next steps necessary to potentially achieve large-scale NDV-vectored vaccine manufacturing.

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Development, optimization, and scale‐up of suspension Vero cell culture process for high titer production of oncolytic herpes simplex virus‐1

Shen,

Burney,

Gilbert

et al. 2023

Biotechnology Journal

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Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, and four OVs have been approved for cancer immunotherapy. However, high yield and cost‐effective production processes remain to be developed for most OVs. Here we developed suspension‐adapted Vero cell culture processes for high titer production of an OV model, herpes simplex virus type 1 (HSV‐1). Our study showed the HSV‐1 productivity was significantly affected by multiplicity of infection, cell density and nutritional supplies. Cell culture conditions were first optimized in shake flask experiments and then scaled up to 3L bioreactors for virus production under batch and perfusion modes. A titer of 2.7 × 108 TCID50/mL was obtained in 3L batch culture infected at a cell density of 1.4 × 106 cells/mL, and was further improved to 1.1 × 109 TCID50/mL in perfusion culture infected at 4.6 × 106 cells/mL. These titers are similar to or better than the previously reported best titer of 8.6 × 107 TCID50/mL and 8.1 × 108 TCID50/mL respectively obtained in labor‐intensive adherent Vero batch and perfusion cultures. HSV‐1 production in batch culture was successfully scaled up to 60L pilot‐scale bioreactor to demonstrate the scalability. The work reported here is the first study demonstrating high titer production of HSV‐1 in suspension Vero cell culture under different bioreactor operating modes.This article is protected by copyright. All rights reserved

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Process Development for Newcastle Disease Virus-Vectored Vaccines in Serum-Free Vero Cell Suspension Cultures

Cited by 17 publications

References 45 publications

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Development and Scalable Production of Newcastle Disease Virus-Vectored Vaccines for Human and Veterinary Use

Development, optimization, and scale‐up of suspension Vero cell culture process for high titer production of oncolytic herpes simplex virus‐1

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