Large-scale production and purification of VLP-based vaccines

Abstract

Virus-like particles (VLPs) hold tremendous potential as vaccine candidates. These innovative biopharmaceuticals present the remarkable advantages of closely mimicking the three-dimensional nature of an actual virus while lacking the virus genome packaged inside its capsid. As a result, an equally efficient but safer prophylaxis is anticipated as compared to inactivated or live attenuated viral vaccines. With the advent of successful cases of approved VLP-based vaccines, pharmaceutical companies are indeed redirecting their resources to the development of such products. This paper reviews the current choices and trends of large-scale production and purification of VLP-based vaccines generated through the baculovirus expression vector system using insect cells.

Production of Japanese encephalitis virus-like particles in insect cells

“…[8][9][10] In this system, following infection with a recombinant nucleopolyhedrovirus (NPV) carrying the foreign gene of interest, lepidopteran insect cells produce extremely large quantities of biologically active proteins with complex folding and posttranslational processing and modifications performed in higher eukaryotes during the very late phase of infection. [11][12][13] Compared with mammalian cells, insect cells are easy to culture, and the growth rates of both cells are comparable.…”

Optimization of Insect Cell Based Protein Production Processes - Online Monitoring, Expression Systems, Scale Up

“…The infection can either be carried out subsequently to cell growth or simultaneously with cell planting into a vessel. For the commercial vaccine production it is crucial to establish an efficient, cost-effective and robust large-scale process to manufacture the required quantities of the protein of interest [115]. Taking the process developed initially in the milliliter or liter scale and scaling it up to industrial production volumes of hundreds or thousands of liters is a challenging procedure.…”

“…Biological process parameters of importance in the BEVS system are generally considered to include cell density at infection, multiplicity of infection, time of infection and physiological state and age of the cells at the time of infection [115].…”

“…Overall, an acceptable equilibrium between the parameters in question has to be found for the specific process and equipment used (see Figure 11). [115,129]. Regardless of the specific system employed, the basic principles for scale up and transfer of a BEVS process into such a system are the same as for the standard stainless steel stirred tank equipment.…”

The MultiBac Baculovirus/Insect Cell Expression Vector System for Producing Complex Protein Biologics

“…In the three decades since these hallmark contributions, baculovirus expression has become a widely adopted technology for academic and industrial applications, in research and development as well as manufacturing, and a wide range of proteins have been made by baculovirus expression vector systems (BEVS) [2,[4][5][6][7]. Multicomponent virus like particles (VLPs) resembling complex virus shells, have been produced successfully with BEVS, including VLPs from bluetongue, rotavirus and others [8][9][10][11]. More recently, the first baculovirus produced proteins have been approved in the therapy or prevention of human disease, including vaccines against influenza …”