Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology

Abstract

Vaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus-like particles, vectored vaccines and chimeric vaccines requires the use - and often the development - of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture.

Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

“…The vast majority of viral vaccines manufactured at present includes whole-cell vaccines in which viruses are either live attenuated or inactivated, and virus-like particles (VLPs), subunit vaccines containing specific parts of the virus with immunogenic properties [5,15]. Examples of attenuated vaccines are those against smallpox, polio (oral vaccine), measles, mumps and rubella, rotavirus gastroenteritis and yellow fever.…”

“…The manufacturing of whole-cell vaccines, based initially on viruses grown in vivo in whole animals or in ovo in embryonated eggs, is now moving towards animal cell culture systems allowing virus propagation in vitro. Chicken embryo fibroblast (CEF) primary cells, human lung-derived Medical Research Council 5 (MRC5) diploid cells, the African green monkey kidney-derived (Vero) and Madin Darby canine kidney (MDCK) cells (continuous cell lines) are the most common cell substrates currently used for vaccine production [5,19]. VLPs can be produced in a variety of cell culture systems including microbial (bacteria and yeasts, mainly Escherichia coli and Saccharomyces cerevisiae), insect (e.g., High Five™ cells from Trichoplusiani used in the Baculovirus Expression Vector System), mammalian (e.g., Chinese hamster ovary (CHO) cells) and -to a lesser extent-plant cells [16,17].…”

“…On an individual level, besides good hygiene practices, protective measures include the use of individual equipment such as facemasks to reduce the spread of airborne viruses with pandemic potential, e.g., influenza A virus (IAV), condoms to prevent the transmission of human immunodeficiency virus (HIV) during sexual intercourse, or else sterile syringes and needles to reduce transmission of blood-borne viruses, e.g., HIV, hepatitis B/hepatitis C virus (HBV/HCV) among injecting drug users. Active immunization, i.e., vaccination, is an indispensable treatment to prevent viral infection [5]. While vaccines against childhood viral illnesses, influenza, polio or hepatitis A/B are routinely administered, the search of efficient and safe prophylactic vaccines against life-threatening diseases such as dengue [6] and Ebola [7] fevers, AIDS [8] and hepatitis C [9], is in continuous progress.…”

Developing high-quality mouse monoclonal antibodies for neuroscience research – approaches, perspectives and opportunities

“…While many sophisticated approaches can be used in immunogen design, guided by intensive efforts in the area of vaccine development, for example see [18], our proximate goal is to generate research reagents for labeling and capturing targets from brain tissue, so our immunogen design is guided by only a few simple considerations. The design of our immunogens is similar to that used by the Human Protein Atlas project except we do not limit the length of our immunogens to 150 amino acids [19].…”

The expanding role of mass spectrometry in the field of vaccine development

“…Appropriately, the vaccine landscape is changing from traditional vaccine approaches to cost‐effective, highly scalable, and safe recombinant vaccines . Using recombinant DNA technology, antigens are expressed in yeast, Escherichia coli , baculovirus expression vector system (BEVS), or mammalian cell lines . Recombinant antigens are engineered to mimic the first step of virus attachment to the cell surface which is mediated by specific glycoproteins.…”