engleski

Accumulation of defective interfering particles as the mechanism of viral vaccine attenuation

Immunization programs have implemented live attenuated vaccines as very effective means of protection against infectious diseases. Live attenuated vaccine against mumps reduced mumps incidence 97 %. Some of the vaccine strains were abandoned due to unwanted side effects and the genetic marker of attenuation has not been identified so far. Our hypothesis was that noninfectious viral particles, in particular defective interfering particles (DIPs), contribute to neuroattenuation. We showed that non-infectious particles of mumps vaccine attenuated neurovirulence of wild type mumps virus. Furthermore, we attenuated a recent wild type mumps virus in Vero cells through 16 passages but already the fifth passage (p5) showed accumulation of DIPs and attenuated neurovirulence in a newborn rat model when compared to second passage (p2). Sequence analysis of p2 and p5 revealed a single mutation in the 5’ untranslated region of the HN gene. The analysis of the expression level of the HN protein showed that this mutation does not affect the expression of the protein. We conclude that passages of the mumps virus in Vero cells for only three passages accumulated DIPs which attenuate neurovirulence. The findings of this study reveal DIPs as a very promising and general neuroattenuating factor which should be considered in the rational design of the new mumps vaccine.

vaccine; attenuation; mumps virus

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