Biological characteristics of genetic variants of Urabe AM9 mumps vaccine virus

The Urabe AM9 mumps vaccine is composed of a mixture of variants distinguis hable by a difference at nucleotide (nt) 1081 of the hemagglutinin-neuramin idase (HN) gene (Brown, E.G., Dimock, K., Wright, K.E., 1996. The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid (aa) 335 of the hemagglutinin-neuraminidase gene with one form associated with disease. J. Infect. Dis. 174, 619-622.). Further genetic and biological variation w as detected in plaque purified viruses from the Urabe AM9 vaccine by examin ing the HN gene sequence, plaque morphology, cytopathic effects and growth in Vero cells, and temperature sensitivity (ts). Infection of Vero cells wi th plaque purified viruses with a G at nt 1081 of the HN gene produced larg e, clear plaques, caused significant CPE early after infection but yielded lower titres of virus than other purified viruses. None of these viruses we re ts. In contrast, half of the plaque purified viruses with an A at nt 108 1 were sensitive to a temperature of 39.5 degrees C. These viruses produced small plaques, caused significant CPE and grew to low titres. Two ts virus es possessed a unique aa substitution at aa 468 of HN. The remaining A(1081 ) viruses were not ts, produced large plaques but little CPE, and grew to t itres 10-fold higher than the G(1081) viruses. Isolates of Urabe AM9 associ ated with post-vaccination illness were similar to these non-ts A(1081) vir uses, but could be further sub-divided into two groups on the basis of a di fference at aa 464 of HN. The post-vaccination isolates may represent insuf ficiently attenuated components of the vaccine, while the G(1081) and ts su bset of A(1081) viruses may be more fully attenuated. (C) 2000 Elsevier Sci ence B.V. All rights reserved.