with limited generations such as Wi-38 and MRC-5 derived human lung fibro-

blasts are used to produce rubella and varicella vaccines. Vero cell line, a con-

tinuous cell line derived from the kidney of the African Green Monkey is used to

produce Salk polio, rabies, rotavirus, and influenza vaccines exploiting micro-

carrier technology to enable industrial scale-up of adherent cell cultures. Other

continuous cell lines that have been adapted to suspension cultures include the

human embryo kidney cells, HEK293 and the primary embryonic retina cells,

PER.C6, two transformed human cell lines, that are used to produce adeno-

vectored vaccines currently licensed for immunization against SARS-CoV-2 in-

fections. Madin-Darby Canine Kidney, MDCK, continuous cell line has been

used as a preferred host for replication of influenza strains and has been adapted

to suspension culture for industrial manufacturing of influenza vaccines. The

development of these different cell culture platforms and the regulatory frame-

work associated with their use for manufacturing viral vaccines is discussed in

Chapter 4, dedicated to cell lines for viral vaccines production.

1.7

MANUFACTURING CHALLENGES OF VIRAL VACCINES

The complex structure of viral vaccines is highly associated with the structure and

biology of the virus causing the infectious diseases. A primary challenge relates to

the size distribution of the viral structures. For example, a measle virus has di-

mensions ranging from 250 to 400 nm, which is largely beyond the 200 nm ster-

ilizing filter pore size. Consequently, cell-culture production of the measles virus

cannot benefit from a final sterilization step, which imposes a complete process

under totally sterile conditions. With recombinant vaccines in the class of the most

FIGURE 1.4 Non-enveloped lytic virus cycle (A) and enveloped virus cycle (B) replication.

Credit to Sven Ansorge for the design of the image.

10

Bioprocessing of Viral Vaccines