Bioprocessing of Viral Vaccines (Amine Kamen)

large quantities of virus is critical. Various cell lines have been used for this type of

vaccine, of which Vero and MRC-5 are prominent (Table 4.2).

Sub-unit vaccines are based on purified antigens, either isolated from whole

virions or produced as single component with recombinant technology. The anti-

gens are highly purified and well characterized. There is no risk of reversion. Sub-

unit vaccines usually require adjuvantation. Several doses and regular boosters are

often needed to confer long-term protection. In the case of purified antigens from

whole virions, cell-line selection is driven by the capacity of the cell line to pro-

pagate large quantities of virus, as is for whole inactivated vaccines. With regard to

recombinant technology, other cell lines are considered. The main criteria for cell

line selection are based on the ability to harbor the gene of interest (i.e., the gene

coding for the sub-unit antigen) and express it appropriately. Several expression

systems have been developed over the past 40 years (for a review, see [4]).

Cell cultures suitable for the development of vaccines can be categorized into three

types: cultures based on (i) primary cells, (ii) diploid cell lines, and (iii) continuous

cell lines (Table 4.3). Primary cells were the first substrates used for the development

of vaccines. Primary cells consist of cells extracted from the tissue source and used

without passage in tissue culture, in accordance with WHO guidance. Primary cells

are not stored (in cell banks), and no longer accepted for the manufacture of new

vaccines. Because the sources of the cells are not homogeneous, manufacturing

consistency is difficult to guarantee; for example, CEFs are isolated from numerous

different chicken flocks to manufacture each batch of vaccine. In addition, the

TABLE 4.2

Cell lines used for marketed inactivated vaccines (non-exhaustive list)

Cell Line

Marketed Vaccine

Disease

CEF (chicken-

embryo fibroblasts)

Rabipur/RabAvert, Encepur (TBE),

FMSE-Immun (TBE)

Rabies, tick-borne encephalitis

MRC-5

Havrix (HAV), Avaxim (HAV), Epaxal

(HAV), VAQTA (HAV), Twinrix (HAV),

Poliovax (discontinued), Imovax (rabies)

Hepatits A, poliomyelitis, rabies

Vero

Poliorix ^∗, Boostrix ^∗, Infanrix ^∗, Pediarix ^∗,

Kinrix ^∗, Quadracel ^∗, Pentacel ^∗,

Pediacel ^∗, IPOL (IPV), IMOVAX Polio,

Adacel (IPV), Celvapan (p-flu), Preflucel

(s-flu), Ixiaro (JEV), Jespect (JEV),

Jenvac (JEV), Jeev (JEV), Encevac

(JEV), VERORAB (Rab), Abhayrab

(Rab), Speeda (Rab)

Poliomyelitis, pandemic and

seasonal flu, Japanese

encephalitis, rabies

Continuous cell lines

MDCK

Optaflu, Flucelvax

Seasonal flu

Note

∗ IPV (inactivated polio virus) antigens are part of these vaccines.

Bioprocessing of Viral Vaccines