David Baltimore (Nobel Prize in 1975) proposed a virus classification in 1971,

focusing on the mode of viral replication. The classification was adopted by the

virologists in parallel to standard virus taxonomy, which is based on evolutionary

history (Chapter 2).

The general steps involved in virus replication include transport of the virus to

the cellular membrane, attachment that might be mediated by specific receptors on

the cell membrane, direct penetration, or endosome-mediated entry in the cell cy-

toplasm and uncoating of the virus structure as early events. Within the cells, the

viral genomic coding sequences will determine the early gene transcription-the

genome replication-late gene transcription/translation as middle events. Finally,

late events include assembly and egress of the virion. Any of these steps and events

are viral specifics but remain essential in determining the kinetics of replication in

the cell-culture production process.

From a processing standpoint, there are two types of viruses, the ones that end

with the lytic cycle (non-enveloped) and the ones that will bud from the cell

surface (enveloped). For example, adenovirus has a lytic infection cycle and

would infect the cells, replicate, accumulate, and then the cell will lyse and the

virus will be released. An example of an enveloped virus is the coronavirus that

will bud off the cells at maturation of the virion. The enveloped or non-enveloped

nature of the virus has critical effects on the selection of upstream and down-

stream processing steps of the associated viral vaccines. Therefore, the nature of

the infectious viral unit and its interaction with the host cell needs to be well

integrated in the design of viral-structure-based vaccines (inactivated, attenuated,

and vectored-vaccines) and the overall manufacturing stream. These mechanisms

will be described in detail in the virology chapter as well as in the specific case

study chapters (Figure 1.4).

Cell culture technology is the most effective mode of production of viral

vaccines. Primary cell lines such as chick embryo fibroblasts are used in the

production of measles and mumps vaccines, whereas human diploid cell lines

VIH

Rabies Virus

Sars Cov-2

Herpes Virus

Papillomavirus

Influenza

Hepatitis B

Rotavirus

Adenovirus

Ebola Virus

FIGURE 1.3 Example of different types of viruses.

Viral vaccines

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