Cell Culture-based Viral Vaccines: Current Status and Future Prospects

Abstract

Cell culture-based viral vaccines are used globally to immunize humans against infections. The cell culture is continuous process of developing substrates for the safe production of viral vaccines. However, increased global demand and strict safety rules for novel vaccines to control and eradicate viral diseases have forced researchers and manufacturers toward cell culture-based vaccines. The choice of cell substrate is a critical step that cannot be generalized for every vaccine formulation, therefore, manufacturers intend to optimize the required processes for particular applications. The recently established cell lines, innovative bioreactor concepts and cultivation schemes are necessary to increase the potential of vaccine production. In this review, we have focused on current cell culture-based viral vaccines and their future prospects. KEYWORDSThe use of vaccines to immunize humans and animals from infectious diseases has been documented for many years. Vaccination has been considered as the best operational approach to prevent infectious diseases, therefore, vaccine research and manufacturing is essential for the eradication and prevention of diseases throughout the world. Presently, more than 50 cell culture-based vaccines for human viral infectious agents are being manufactured, with many more at the research or developmental stages. Vaccination involves the administration of inactivated or attenuated infectious agents or subunit vaccines, which delivers the antigenic structures and provokes the adaptive immune system to ensure effective response against particular infections. Another method for the production of viral vaccines, egg-based production, is still the most widely used method to generate approximately 500 million vaccine doses and has been used for more than 60 years [1]. The increased vaccine demand and the potential threats of epidemics and pandemics have boosted the needs to introduce new manufacturing approaches for viral vaccines. The egg-based viral vaccine production is insufficient to fulfill the vaccine demands in cases of epidemics and pandemics due to unavailability of eggs. The egg-based vaccine production is only capable of an estimated yield of one vaccine dosage per one to two eggs. The current manufacturing capacity has to be projected for the production of almost 1420 million doses [1], therefore, it is essential to increase the existing vaccine production by a factor of 1.5 per year to immunize the global population against viral infections that cannot be achieved only by the egg-based system [2]. Therefore, many countries have initiated

Immunomodulatory Strategies for Parapoxvirus: Current Status and Future Approaches for the Development of Vaccines against Orf Virus Infection

“…However, ORFV penetrates a susceptible host and temporarily replicates transiently by undermining host immunity [117]. Once the viral pathogen is internalized, the cells of the innate immune system such as neutrophils, MHC class II-dendritic cells (DCs), and natural killer (NK) cells are constantly recruited to the sites of infection to capture the viral antigens, which facilitates the migration of the captured antigens to the peripheral lymph node where the antigen presentation to newly recruited naïve T-cells and memory cells take place [82,[117][118][119].…”

“…However, ORFV penetrates a susceptible host and temporarily replicates transiently by undermining host immunity [117]. Once the viral pathogen is internalized, the cells of the innate immune system such as neutrophils, MHC class II-dendritic cells (DCs), and natural killer (NK) cells are constantly recruited to the sites of infection to capture the viral antigens, which facilitates the migration of the captured antigens to the peripheral lymph node where the antigen presentation to newly recruited naïve T-cells and memory cells take place [82,[117][118][119]. The dendritic cells (DCs) facilitate the transport of the internalized virus to the lymph nodes for further proliferation [119] and the presentation of specialized cytokines such as granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin-1β (IL-1b), interferon-α (IFN-α), and IL-8, and IFN-γ [54,56,73,80,120].…”

“…Therefore, blockage of the activities of both the innate and acquired immune response is one of the main strategies in successful ORFV infections. However, the functional mechanisms of GIP in ORFV pathogenesis and virulence are yet to be determined [84,117,160].…”

Animal Cell Lines as Expression Platforms in Viral Vaccine Production: A Post Covid-19 Perspective

“…2,10,13 Thus, a driving force has emerged for the use of the animal cell culture technique, in which studies can be carried out at the cellular level by moving away from the structure of a whole organism, in the production of biological products such as vaccines. 4,6,14,15 In particular, "cell lines" developed based on the integrated progress of genetics, molecular biology, and cell culture techniques stand out in this sense. 6,12,14,15 In addition to the cell lines that have been used in production with proven safety for many years, improvements are constantly being made in industrial production thanks to their derivatives obtained as a result of various molecular modifications and newly developed cell lines.…”

“…The production methods of these vaccines, developed against both bacterial and viral pathogens, vary greatly. Especially in vaccines developed against bacterial pathogens, the disease agent itself or the bacterial toxin associated with the disease can be produced directly, whereas for viral pathogens the process is more complex. − This is because viral pathogens, due to their intracellular parasitic nature, do not have the mechanisms to reproduce, so they need a suitable host which they can replicate themselves. ,,, Although in the historical process, live animals such as cattle were first used to propagate the viral agent, the drawbacks of this practice were revealed over time. ,, Thus, a driving force has emerged for the use of the animal cell culture technique, in which studies can be carried out at the cellular level by moving away from the structure of a whole organism, in the production of biological products such as vaccines. ,,, …”