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Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice

¹ Discipline of Microbiology, School of Biomedical and Chemical Sciences, The University of Western Australia, WA, Australia
² Division of Microbiology and Infectious Diseases, PathCentre, Perth, WA, Australia
³ Department of Microbiology and Parasitology, School of Microbial and Molecular Sciences, The University of Queensland, QLD, Australia
⁴ Division of Virology, Telethon Institute for Child Health Research, 100 Roberts Road, Subiaco, WA 6008, Australia

Correspondence
Peter McMinn (at address 4)
peterm{at}ichr.uwa.edu.au

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.

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