Some aspects of the monkey neurovirulence test used for the assessment of oral poliovirus vaccines.
Twelve years of experience in three control laboratories with 8,000 macaca monkeys for the testing of 204 monovalent lots of the three types of oral poliovirus vaccine (OPV), have shown that the new monkey neurovirulence test (MNVT) adopted by the World Health Organization (WHO) is a reproducible and sensitive assay likely to ensure the safety of this vaccine in humans. When the test vaccine and the appropriate homotypic reference vaccine were tested in a single group of monkeys, the concurrent use of the reference vaccine considerably increased the reproducibility of the test. The usefulness of the WHO MNVT was further demonstrated in our laboratory when the test was applied to types 1 and 3 vaccine strains that were passaged serially in the intestinal tract of infants. The test was suitable for detecting increased monkey neurovirulence in these human passage strains that did not reach the level of neurovirulence of the "wild" types 1 and 3 strains tested concurrently (except human passage no. 7 of the type 3 vaccine that multiplied for a cumulative 109 days in seven infants). The statistical analysis of the data showed that the old intrathalamic (IT) assay used for many years in our laboratory was considerably less sensitive than the intraspinal WHO MNVT; a test vaccine with a two-fold increase in monkey neurovirulence showed a 41% chance of failing in the IT test (using 30 monkeys per vaccine), while this chance increased to 99% in the WHO assay (using 12 monkeys for types 1 and 2 vaccines and 20 monkeys for type 3 vaccine). Indeed, three of seven type 3 lots tested in our laboratory with both assays failed in the WHO assay but all lots passed in the IT test. Since the introduction of the WHO MNVT in Canada and the United Kingdom, the number of vaccine-associated paralytic poliomyelitis cases in the population continued to remain at a low level.
Bureau of Biologics, Health and Welfare Canada, Tunney's Pasture, Ottawa, Ontario.
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D000818:Animals; D001681:Biological Assay; D002170:Canada / Q000453:epidemiology; D002521:Cercopithecus; D004739:England / Q000453:epidemiology; D005243:Feces / Q000382:microbiology; D006801:Humans; D007223:Infant; D008251:Macaca; D008828:Microbiological Techniques / Q000592:standards; D011051:Poliomyelitis / Q000453:epidemiology / Q000209:etiology*; D017955:Poliovirus / Q000302:isolation & purification / Q000472:pathogenicity*; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects / Q000633:toxicity*; D012015:Reference Standards; D012449:Safety; D012680:Sensitivity and Specificity; D014481:United States / Q000453:epidemiology; D014774:Virulence; D014944:World Health Organization
D011055:Poliovirus Vaccine, Oral