Vero cell upstream bioprocess development for the production of viral vectors and vaccines

Abstract

The Vero cell line is considered the most used continuous cell line for the production of viral vectors and vaccines. Historically, it is the first cell line that was approved by the WHO for the production of human vaccines. Comprehensive experimental data on the production of many viruses using the Vero cell line can be found in the literature. However, the vast majority of these processes is relying on the microcarrier technology. While this system is established for the large-scale manufacturing of viral vaccine, it is still quite complex and labor intensive. Moreover, scale-up remains difficult and is limited by the surface area given by the carriers. To overcome these and other drawbacks and to establish more efficient manufacturing processes, it is a priority to further develop the Vero cell platform by applying novel bioprocess technologies. Especially in times like the current COVID-19 pandemic, advanced and scalable platform technologies could provide more efficient and cost-effective solutions to meet the global vaccine demand. Herein, we review the prevailing literature on Vero cell bioprocess development for the production of viral vectors and vaccines with the aim to assess the recent advances in bioprocess development. We critically underline the need for further research activities and describe bottlenecks to improve the Vero cell platform by taking advantage of recent developments in the cell culture engineering field.

Overview on Chikungunya Virus Infection: From Epidemiology to State-of-the-Art Experimental Models

“…Likewise, Singh and colleagues characterized two peptidomimetic compounds as CHIKV protease inhibitors in a BHK-21 cell model and were able to propose their mechanism of action on the replicative process (Singh H. et al, 2018). Vero-E6 was used to study the entry mechanism of a candidate CHIKV vaccine, as well as the inhibition of virus-cell binding in infected cultures treated with CHIKV antibodies (Fritz et al, 2012;Shen et al, 2019;Kiesslich and Kamen, 2020;Weiss et al, 2020). Garg et al (2020) implemented virus like particles (VLPs) produced in 293T cells as a model for CHIKV vaccines, highlighting a new role of this cell in CHIKV research.…”

The Rise of Vectored Vaccines: A Legacy of the COVID-19 Global Crisis

“…The methods for production and purification of vaccine vectors should also be kept in mind, considering that they need to be scalable to industrial settings [9,[27][28][29]. Indeed, most vectors are easily produced and scaled-up [20,30].…”

Haplotype-resolved de novo assembly of the Vero cell line genome

“…In addition, gene-editing tools have been used to create Vero suspension cell lines, which are considered to facilitate bioprocess development efforts. Nevertheless, singular genome modifications did not seem to lead to successful and sustainable results 1 . Using the annotated genome presented here, further studies can be conducted to investigate suspension adaptation efforts, for example, large-scale screens could identify if a combination of modifications is needed.…”

“…Originated from a female Chlorocebus sabaeus (African Green Monkey) kidney, the Vero cell line represents the most widely used continuous cell line for the production of viral vaccines with over 40 years of experience 1 . This includes the development and production of vaccines against dengue fever, influenza, Japanese encephalitis, polio, rabies, rotavirus, smallpox and more recently, Ebola (using a recombinant vesicular stomatitis virus) [2][3][4] .…”