The monkey safety test for neurovirulence of yellow fever vaccines: the utility of quantitative clinical evaluation and histological examination.
Two different derivatives of the 17D strain of yellow fever (YF) vaccine virus, i.e. ALV-free seed virus 6676 and three consecutive vaccine lots, A, B and C, obtained from another seed, were compared in monkey neurovirulence tests using rhesus and cynomolgus monkeys. In addition the ALV-contaminated seed lot AB 237 was safety tested in rhesus monkeys. According to WHO clinical criteria for acceptability, lots A, B, C and lot AB 237 consistently passed, while lot 6676 passed some tests and failed others. In the same tests, quantitative clinical evaluation and histological examination of CNS gave more definitive and consistent data on the higher degree of neurovirulence of lot 6676. Especially differentiating histological findings were obtained from some anatomical structures of the CNS ('discriminator areas') and almost no difference was found between the products in the structures apparently most susceptible to YF virus ('target areas'). Although some of the target and discriminator areas were different, cynomolgus monkeys were not less susceptible than rhesus monkeys to YF vaccine virus. The use of a quantitative method of scoring specific lesions in CNS of monkeys and the comparison of the average scores of a YF vaccine lot under study with a 'reference' vaccine, which has proven to be safe and effective in humans, should provide for a more reproducible method of assessing vaccine neurovirulence.
Levenbook
I S
IS
Office of Biologics Research and Review, FDA, Bethesda, Maryland 20892.
Pelleu
L J
LJ
Elisberg
B L
BL
D000818:Animals; D008252:Macaca fascicularis; D008253:Macaca mulatta; D009420:Nervous System / Q000276:immunology* / Q000473:pathology; D009461:Neurologic Manifestations / Q000276:immunology* / Q000473:pathology; D014613:Vaccines, Attenuated / Q000009:adverse effects*; D014774:Virulence; D015004:Yellow Fever / Q000517:prevention & control*
D014613:Vaccines, Attenuated