are usually sought. For this purpose, conformational antigens must be produced.

When a cell-mediated response is anticipated, antigens with sequential epitopes can

be designed. These questions are more thoroughly addressed in Chapter 3.

In addition, the variability of the antigen should be considered to generate im-

munity to natural variants or strains of the virus, and hence to confer the broad or

cross-strain protection.

The knowledge arising from immunology and specific viral diseases have led to

three major types of marketed vaccines: live-attenuated vaccines, whole-inactivated

vaccines, and sub-unit vaccines.

Live-attenuated vaccines consist of attenuated viruses reproducing aspects of

natural infection but without the disease symptoms. They do not require adjuvant.

Because the attenuated virus can replicate in the vaccine recipient, the dose amount

is generally low. The immune response is generally broad because the attenuated

virus contains numerous antigens and allows a better presentation to activated

humoral and cellular immunity. One potential drawback of live-attenuated viruses is

their potential reversion back to wild type. This is particularly the case for viruses

with genomes consisting of positive RNA strands, such as the poliovirus. Reversion

of OPV (oral poliomyelitis vaccine) has been well documented [3].

For live-attenuated vaccines, the selection of a cell line is highly dependent on its

susceptibility to viral infection. Three main cell lines have now been used for

several decades; CEF (chicken-embryo fibroblasts), MRC-5 and Vero (Table 4.1).

Whole-inactivated vaccines are made from viruses propagated in cells and then

further purified to obtain antigens. The immunogenic dose (by virus-particle

equivalent) is usually high in comparison to live-attenuated vaccines. This type

of vaccine is usually adjuvanted, typically with aluminium salts. Because higher

amounts of antigen are typically required, the capacity of the cell line to propagate

TABLE 4.1

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

Cell Line

Marketed Vaccine

Disease

CEFs (chicken

embryo

fibroblasts)

Priorix (Me-Mu), Attenuvax (Me),

Mumpsvax (Mu), Trimovax (Me),

ProQuad (Me-Mu)

Measles and mumps

MRC-5

Priorix (Ru), Tresivac (MMR),

Trimovax (Ru), Varilrix (Va), Biopox

(Va), ProQuad (Va), Zostavax (Va),

Varivax (Va), Priorix-Tetra (va)

Mumps, measles, rubella, varicella

or chickenpox

Vero

Rotarix, Rotateq, ACAM2000

(smallpox), IMOJEV (JEV), OPV

Gastroenteritis due to rotavirus,

smallpox, Japanese encephalitis,

poliomyelitis

Wi-38

MeruvaxII (Ru), ProQuad (Ru),

Adenovirus Type 4 and Type 7

Vaccine Live Oral

Rubella, adenoviruses

Cell lines for vaccine production

59