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This article was published in 1965
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Modern Vaccine Production

ARTHUR WEBSTER, B.V.Sc., Northmead.

As with other pursuits, the development of vaccines and the methods of their production does not progress, at least in the experience of one manufacturer, with a steady, even flow. After a season of comparative quiescence a sudden surge, whether from a new appreciation of possibilities or from the availability of new techniques, it is difficult to know, leaves one with a flock of ideas with which it is seemingly impossible to cope.

The development of tissue culture growth as a reliable routine procedure has opened a vast new field and made possible improvement in long-established vaccines. It leads to less contamination with redundant protein content, less diversion of recipient animal reaction from virus antigen and, in particular, nice control of degrees of virulence by passage in homologous or foreign tissue, this without too great a loss of value as an antigen. The development of tissue culture as a method of bulk production poses mechanical problems; the progress from gallon bottles to thousand-gallon tanks for bacterial vaccines took 20 years; it is hoped with tissue culture to attain comparable bulk output much more quickly. Another attraction of these methods is the elimination of costly eggs and production animals in an endeavour to counter the ever-rising costs of all other components and services between manufacturer and user.

One cannot but marvel that diseases, whose existence is unsuspected, can be recognised, be recorded in our own country and in a few years be accepted as of major importance and the source of great loss. Leptospirosis and Infectious Bronchitis of poultry are examples, and Infectious Bovine Rhinotracheitis appears, judging by overseas reports, to have occupied at least the first two categories.

While there are still unknown traps in virus combination and mutation we feel that, with animals, in the case of widespread enzootic disease causing economic loss, protection should be initiated with live virus vaccines attenuated as far as consistent with practical antigenic value. Having mitigated the loss and held spread of disease by this means, research may be directed toward, first, less virulent to avirulent viruses, and finally to elimination by use of killed vaccines combined with husbandry methods.

Familiarity with virus vaccines has complicated matters by emphasising the danger of unwanted contaminants being included with the prophylactic virus. The development of human live-virus vaccines has led to exhaustive measures for the exclusion of such "wild" viruses and this lead will have to be followed in the animal sphere.

For many years, Fowl Pox Vaccine was made with fowls and eggs selected for apparent freedom from disease, particularly with leucosis in mind, and, in fact, no evidence has been brought forward to suggest spread in this manner. However, desire to be above criticism in this respect and, even in some small measure, consumer demand is enforcing known freedom from pathogens, and the establishment and perpetuation of disease-free sources of eggs and animals furnishing tissues for culture.

One method of reducing the burden of numbers of these animals is the use of cell lines; that is, serial culture of cells after the manner of bacterial cultures. It is possible to establish these, with persistence and good fortune, from a wide variety of tissues, and in time have a sufficient diversity to accommodate all required viruses. Having once established a cell line it may be shown by exhaustive test to be safe before use in propagation of the virus. The somewhat remote but theoretically possible danger of carcinogenic properties in these cell lines has not so far had any support in field use in pets, but once large numbers of pet animals have safely reached the end of their life span, valuable evidence for use in humans may be furnished.

A point not widely appreciated is that not only is the cell line, on which the virus vaccine is grown, suspect, but once having been so grown the virus itself may possibly diverge to carcinogenic code.

In the "Golden Age" of bacteriology, a handful of enthusiasts made remarkable progress in very few years.

We are now experiencing a similar wave of success in virology, with the difference that the explorers are organised specifically for the purpose, being very much greater in numbers and much better equipped, so that the flood of new information presents a major problem of selection for the would-be manufacturer of better biologicals.

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