Although 80% of the influenza vaccines are still produced using embryonated

egg technology [18], there is a trend to use cell culture technologies in all other

cases of traditional viral vaccines including rabies, yellow fever, poliomyelitis,

measles, mumps, rubella, adenovirus, Japanese encephalitis, Hepatitis A, varicella,

rotavirus, human papilloma virus, dengue, zoster, and Ebola vaccines.

With the exception of mRNA vaccines, all COVID-19 vaccines approved or in

advanced clinical trials are cell-culture produced vaccines indicating a solid trend for

establishing cell culture advanced technologies for manufacturing viral vaccines.

1.6

CELL-CULTURE PRODUCTION PROCESSES

The cell-culture production process is designed integrating the basic knowledge on

virology including the viral structure, its biology, and the viral replication cycle will

be extensively described in Chapter 2 as basic virology for process design. Viruses

are biological structures with sizes ranging from 20–300 nm, containing DNA or

RNA coding for proteins necessary for replication, including non-structural and

structural proteins contributing to a “shell” capsid that might be an icosahedron or

helical asymmetrical capsid, and eventually an envelope as it is the case for HIV,

SARS-CoV, and influenza viruses, for example, or non-enveloped (adenovirus,

adeno-associated virus, or human papilloma virus) (Figure 1.3).

FIGURE 1.2 An embryonated chicken egg showing the different compartments in which

viruses may grow. The different routes by which viruses are inoculated into eggs are

indicated.

8

Bioprocessing of Viral Vaccines