Articles

Continuously Cultured Tissue Cells and Viral Vaccines

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Science  04 Jan 1963:
Vol. 139, Issue 3549, pp. 15-20
DOI: 10.1126/science.139.3549.15

Abstract

1) Continuously cultured tissue cells afford numerous potential advantages for the propagation of viruses to be used in vaccines.

2) Because continuously cultured tissue cells sooner or later become capable of growing into neoplasms when transplanted into a suitable host, every possible precaution should be taken to ensure that viral vaccines grown in cell cultures are free from living cells and cell particles larger than 0.5 to 1.0 micron.

3) The radical abnormalities that occur in cell lines derived from neoplasms and those that develop sooner or later in cell lines derived from normal tissue cannot be ignored. However, no evidence has been recorded (i) that untoward consequences follow administration of cell-free preparations from such cultures to humans or (ii) that oncogenic or other viral activity is associated with the ability of cells of these lines to grow into neoplasms when transplanted into a suitable host. It seems very unlikely, nevertheless, that acceptance could be won at present for the general use of a live-virus vaccine prepared from a virus grown in cells showing evidences of malignancy. This conclusion is based more on psychological and public relations considerations than on the available scientific information, which, however, needs considerable augmentation. In this connection, careful consideration should be given to the question whether the absence of the cited kinds of abnormalities from a continuously cultured cell system is a sufficient indicator of freedom from oncogenic potential. In the absence of unfavorable data, we judge that present knowledge does not preclude judicious extension of clinical trials, in volunteers, of appropriately filtered and otherwise controlled experimental live-virus vaccines grown in carefully selected continuously cultured cell systems. Only in this way can sufficient data be collected, and adequate criteria be developed, to define eventually the conditions for acceptability of such preparations for general administration to humans.

4) Every possible effort should be devoted to the development of non-oncogenic and otherwise acceptable cell lines from normal tissues for use in viral vaccine production. It is suggested that exploratory studies begin with continuously cultured mixed-cell populations in the diploid state and stabilized cloned cultures. Criteria for the selection and monitoring of cell lines, and progressive steps leading to large-scale application are outlined.

5) If the need for immunization against a particular viral disease should be deemed sufficiently urgent, and if no practicable alternative were available, serious consideration might be given to a vaccine prepared by inactivating the virus, grown in such a selected stabilized cell line as HeLa or human skin epithelium. The conditions of preparation would have to be such as would inactivate the most resistant known viruses and infective nucleic acids with a generous margin of safety.

6) Principal areas needing intensified research emphasis are indicated.

The authors were appointed by the Director, National Institutes of Health (NIH), in January 1962, as a Task Force on Tissue Culture Viruses and Vaccines, to review current knowledge of problems and trends relating to the use of continuously cultivated cells in the production of viruses to be used in manufacturing vaccines and similar preparations, and to identify areas requiring additional research emphasis. This report was submitted to the Director, NIH, on 4 September 1962. Since it is necessarily a compendium of generally known information, personal communications of unpublished data, and individual judgments based on specialized knowledge, the customary bibliography was deemed to be impracticable. After completion of this report, an independent discussion of some of the same problems was made available to us as a Report (MHO/PA/140.62) by the Scientific Group on the Human Diploid Cell, to the Director General, World Health Organization, Geneva.

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