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Work package 4

Biology of mumps virus and design of safe vaccines

Live attenuated virus vaccines have helped control of a number of diseases caused by RNA viruses. Their success may stem from their ability to effectively activate the innate and acquired immunity. However, the main challenges in the generation of safe, live-attenuated vaccines against RNA viruses are posed by the intrinsically high mutation rates of RNA viruses which, together with the selective pressures exerted by the environment to enhance viral fitness, often result in the reversion of vaccine strains into the wild type phenotype, which leads to infrequent but severe vaccine-associated disease (Kenney et al., Vaccine, 2011). One class of RNA viruses that harbors a broad spectrum of serious pathogens which continuously evolve and re-emerge are the viral family Paramyxoviridae.

Mumps virus, belonging to the Rubulavirus genus within Paramyxoviridae, was identified as the etiological agent of the disease more than 70 years ago, but there are very few data about the molecular basis of neurotropism, neurovirulence and molecular markers of attenuation for this paramyxovirus (Sauder et al,. J Virol, 2011) Although nearly eliminated from most developed countries at the turn of the century, over the past 6 years mumps did resurge globally as an important public health issue with outbreaks occurring in highly vaccinated populations (WHO MMWR Morb. Mortal. Wkly. Rep. 2010) making it an attractive target for research and vaccine design. A prerequisite for designing a model mumps vaccine is to create an attenuated mumps virus with a stable genome and well understood virulence.

Therefore, here in this workpackage we are working on:

  1. Construction of an attenuated mumps virus and determination of (i) the cause of virulence, (ii) ways to control the stability of the attenuated phenotype and (iii) the optimal conditions for achieving high viral titers.
  2. Design and construction of a recombinant mumps virus from the backbone of the attenuated mumps virus generated under (1) carrying target glycoprotein genes of the RSV (G protein and F protein) and HCV (E1 and E2 proteins). Such a vector vaccine would induce both humoral and cellular immunity.
  3. Analysis of the immunological and safety profiles of both the attenuated mumps vaccine and recombinant mumps-virus based vaccine.