History Of Viral Vaccines

The first vaccine (Table 1.1), Jenner's smallpox (1798), was produced on the skin of living animals and was a very 'dirty' preparation. The next vaccine, rabies (1885) produced in spinal cord preparations, was equally contaminated with host proteins and caused severe anaphylactic shock and other side effects. The need for cleaner and safer vaccines led to the use of embryonated chicken eggs (yellow fever, 1935; influenza, 1936) and although an improvement, these preparations were still often contaminated with microorganisms. Thus the use of cultured primary cells was seen as a great breakthrough in terms of microbiological quality and purity (i.e. low levels of extraneous contaminating protein). However, subsequent research showed that monkey kidney cells were host to a wide range of intrinsic viruses such as a collection of simian viruses (SV), herpes B virus, etc. Some of these, like SV40, were known to be transforming viruses and thus concerns were felt over the possibility of introducing tumorigenic material with the vaccine. In fact a batch of polio vaccine contaminated with SV40 was given to vaccinees, causing considerable anxiety, but a follow-up over subsequent years has thankfully shown no increased incidence of cancer in this group over that in the population as a whole. This, together with incidents of insufficient inactivation,

Medicines from Animal Cell Culture Edited by G. Stacey and J. Davis © 2007 John Wiley & Sons, Ltd

Table 1.1 History of viral vaccines.

Key Development

Period

Examples

First viral vaccines

Before 1900

Smallpox (1798) from animal skin

Rabies (1885) from spinal cord

Safer primary cell substrates

1930s-1950s

Yellow Fever (1935) from chick eggs

Influenza (1936) from chick eggs

Polio (1954) from primary monkey cells

Controlled cell substrates

1960s

Measles (1963)

Mumps (1967)

Rubella (1969)

Improved scale-up technology

1970s

Microcarrier culture

Recombinant solution

1980s onwards

Hepatitis (1986)

HIV, herpes, CMV, etc.

slowed down the development of new vaccines considerably. Human vaccine manufacture from animal cells only accelerated when the human diploid cell, WI-38, was introduced (Hayflick & Moorhead 1961). This cell strain was shown to be free of all known intrinsic viruses, behaved as a normal (non-tumourigenic) cell in culture, had reproducible growth characteristics, and aged normally before dying out after 50-60 population doublings. Another great advantage was that a batch of cells could be grown up, quality controlled, and hundreds of replicate ampoules banked in liquid nitrogen. Each ampoule could be used for just one vaccine batch and all ampoules would behave in an identical manner. The concept of 'cell banking' is a key milestone in the development of animal cell biotechnology, and one only has to look to the 'HeLa scandal' to know why.

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