Assessment of packed bed bioreactor systems in the production of viral vaccines

Nicolas Havelange,Kapil Maithal,Stéphanie Dubois,Sankar Rao Macherla,Ramya Rajendran,Siva Kumar Vuppu,Elaiyaraja Manickam,Rajendra Lingala,Bala Obulapathi Bandi

doi:10.1186/s13568-014-0025-z

Abstract

Vaccination is believed to be the most effective method for the prevention of infectious diseases. Thus it is imperative to develop cost effective and scalable process for the production of vaccines so as to make them affordable for mass use. In this study, performance of a novel disposable iCELLis fixed bed bioreactor system was investigated for the production of some viral vaccines like Rabies, Hepatitis-A and Chikungunya vaccines in comparison to conventional systems like the commercially available packed bed system and roller bottle system. Vero and MRC-5 cell substrates were evaluated for growth parameters in all the three systems maintaining similar seeding density, multiplicity of infection (MOI) and media components. It was observed that Vero cells showed similar growth in all the three bioreactors whereas MRC-5 cells showed better growth in iCELLis Nano system and roller bottle system. Subsequently, the virus infection and antigen production studies also revealed that for Hepatitis-A and Chikungunya iCELLis Nano bioreactor system was better to the commercial packed bed bioreactor and roller bottle systems. Although for rabies antigen production commercially available packed bed bioreactor system was found to be better. This study shows that different bioreactor platforms may be employed for viral vaccine production and iCELLis Nano is one of such new convenient and a stable platform for production of human viral vaccines.

Highlights

Viral vaccines are usually produced by anchoragedependent cell lines
Here we have evaluated the feasibility of using the novel iCELLis Nano disposable bioreactor system for the production of some viral vaccines such as Rabies, Hepatitis-A and Chikungunya vaccine in Vero and MRC-5 cells
Hepatitis-A virus (HM-175) and Chikungunya virus (CHIK 181/Clone 25) were received from Centre for Disease Control, Atlanta and United States Army Medical Research Institute of Infectious Diseases, Frederick, MD respectively. These viruses were propagated in MRC-5 cells Virus maintenance medium (VMM) which consisted of H-MEM medium with 3% Fetal bovine serum (FBS), (Moregate, Australia)

Summary

Introduction

Viral vaccines are usually produced by anchoragedependent cell lines. The use of improved modern tissue culture technology for the large-scale propagation of adherent cells is required to overcome the scalability issue. Drugmand et al (2009) have shown that iCELLis Nano is a scale-down version of larger production units and it is a right tool to benchmark with traditional cell culture systems Viral diseases such as Rabies, Hepatitis-A and Chikungunya are widely prevalent in most of the developing countries (Bourhy et al 2010, Franco et al 2012, Edelman et al 2000; Sreekumar et al 2010). We observed two fold increases in the antigen yield and double the number of vaccines doses for Hepatitis-A and Chikungunya vaccines from iCELLis Nano in comparison to other two systems evaluated in the study This could help to reduce the production cost and manufacturing time. This data indicates that iCELLis Nano is a convenient and stable platform for the production of Hepatitis-A and Chikungunya vaccines

Materials and methods

Result

Findings

Discussion