Immunisation with gamma globulin to Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: Evaluation in a mouse model

Abstract

In northwestern Australia, the flavivirus Murray Valley encephalitis (MVE) poses a significant health risk to infants in some aboriginal communities, particularly during each wet season. While there are too few cases to warrant the development of a vaccine against MVE, a safe, effective prophylaxis for these children is still urgently required. The use of passive transfer of human gamma globulin to MVE or immunisation with a vaccine to the closely related Japanese encephalitis (JE) virus were investigated as potential strategies. When 40 microg of IgG was purified from MVE-immune human sera and transferred to 3-week-old mice, the animals were protected from lethal IP inoculation with MVE virus while still producing a detectable immune response to the virus. Similarly, sera from adult mice infected sublethally with MVE or JE virus provided significant protection against MVE infection. However, sera from mice sublethally infected with the related Kunjin or immunised with the inactivated JE vaccine (Biken) provided no protection against MVE challenge. In fact, mice immunised passively with the latter appeared to succumb to MVE challenge more rapidly than mice that received serum from unimmunised animals, suggesting that antibody to the vaccine had accelerated the progression of disease. These preliminary trials in mice indicate that passive immunisation with human gamma globulin has the greatest potential as a strategy for MVE prophylaxis, whilst the apparent enhancement of MVE by antibodies to the JE vaccine requires further investigation, with particular reference to current vaccination programs in areas of Australia and Papua New Guinea, where both JE and MVE occur.

West Nile virus infection of horses

“…However, antibody-enhancement of disease is a phenomenon observed in some flavivirus infection models. Thus, vaccination against JE did not protect against but enhanced MV encephalitis [20]. This phenomenon is due to the presence in serum of sub-neutralising levels of heterologous antibodies and has been described in vitro [36] and recently in vivo [96].…”

“…This is surrounded by a host-cell envelope modified by the insertion of two virus encoded proteins, the major envelope protein E (53 kDa) and the membrane protein M (8 kDa). The latter derives from a precursor protein, prM (18)(19)(20), that is cleaved before virion release from the infected cell [18,31].…”

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

“…Broom et al (2000) examined several strategies to protect against MVE using a mouse model. These studies included (1) passive immunization of mice with homologous (MVE) immune serum and (2) induction of cross-protective immunity by immunization with the JE (Biken) vaccine.…”

Short report: absence of protective neutralizng antibodies to West Nile virus in subjects following vaccination with Japanese encephalitis or dengue vaccines.

“…Immunization of mice with inactivated JE vaccine failed to protect against challenge with Murray Valley encephalitis, while passive transfer of their immune sera may have enhanced disease. 11 However, serial or simultaneous immunization with replicating dengue viruses also did not generate WN virus-specific neutralizing antibodies. Evaluation of cross-reactive cellular responses to WN virus in these individuals may be illuminating.…”